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Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet

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Title: Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet
Language: English
Authors: Guest, J. F., Bai, J. J., Taylor, R. R., Sladkevicius, E., Lee, P. J., Lachmann, R. H.
Source: Journal of Intellectual Disability Research. Jun 2013 57(6):567-579.
Availability: Wiley-Blackwell. 350 Main Street, Malden, MA 02148. Tel: 800-835-6770; Tel: 781-388-8598; Fax: 781-388-8232; e-mail: cs-journals@wiley.com; Web site: http://www.wiley.com/WileyCDA/
Peer Reviewed: Y
Page Count: 13
Publication Date: 2013
Document Type: Journal Articles
Reports - Research
Descriptors: Foreign Countries, Diseases, Metabolism, Dietetics, Comorbidity, Access to Health Care, Costs, Longitudinal Studies, Patients, Health Services, Databases, Symptoms (Individual Disorders), Disabilities, Nutrition, Drug Therapy, Hospitals
Geographic Terms: United Kingdom
DOI: 10.1111/j.1365-2788.2012.01568.x
ISSN: 0964-2633
Abstract: Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. Results: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between 21 000 pounds and 149 000 pounds, depending on the amount of prescribed nutrition they received. Conclusion: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet. (Contains 6 tables and 3 figures.)
Abstractor: As Provided
Number of References: 29
Entry Date: 2014
Accession Number: EJ1013026
Database: ERIC
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  Value: <anid>AN0087564270;eul01jun.13;2018Jul09.14:14;v2.2.500</anid> <title id="AN0087564270-1">Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine-restricted diet. </title> <p>Background  To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine‐restricted diet for life. Methods  A computer‐based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co‐morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. Results  Patients who remained on a phenylalanine‐restricted diet accounted for 38% of the cohort. Forty‐seven per cent of patients discontinued their phenylalanine‐restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine‐restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between £21 000 and £149 000, depending on the amount of prescribed nutrition they received. Conclusion  The findings suggest that the majority of patients with PKU were under‐treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long‐term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.</p> <p>cost; phenylalanine‐restricted diet; phenylketonuria; PKU; resource use; budget impact</p> <p>Classic phenylketonuria (PKU) is a recessively inherited disorder of amino acid metabolism in which the liver enzyme, phenylalanine hydroxylase is absent or significantly reduced in activity (Williams et al. 2008). This defect causes raised blood concentrations of the amino acid phenylalanine and a relative deficiency of tyrosine. Plasma levels of phenylalanine can reach 1000–2000 µmol/l, whereas normal levels are 40–120 µmol/l (MRC Working Party on Phenylketonuria 1993a; Kayaalp et al. 1997; Williams et al. 2008).</p> <p>The prevalence of PKU in the UK is one in 10 000 live births, but there are world‐wide variations (Hardelid et al. 2008). For example, in Ireland the incidence is twice that in the UK (Guldberg et al. 1995). Irreversible retardation can be prevented if affected infants are put on a low‐phenylalanine diet within 21 days of birth, and there is good dietary compliance during the critical period of early development. Moreover, if adequate phenylalanine concentrations can be maintained throughout childhood, children with PKU can expect to have normal intelligence (Thompson et al. 1990; NIH Consensus Statement 2000; NSPKU 2004). Normal intelligence has been shown to be closely related to the quality of blood phenylalanine control, particularly during pre‐school and early school years (Bouchlariotou et al. 2009).</p> <p>In the UK the published guidelines encourage PKU sufferers to remain on a protein‐restricted diet for life, although the length of diet has been the subject of much discussion in recent years (NSPKU 2004). It was initially thought that the restricted diet could be discontinued once the main neuronal developments of the brain had occurred at around 8 years of age. However, some studies report severe deterioration in brain development in children under 12 years and cognitive deterioration in young adults who had stopped their low‐phenylalanine diet (MRC Working Party on Phenylketonuria 1993b; Potocnik & Widhalm 1994). Hence, the degree to which blood phenylalanine levels should be controlled remains controversial (Arnold 2009) and the optimal duration of dietary restriction necessary to avoid the adverse effects of hyperphenylalaninaemia is also unclear (Poustie & Rutherford 2000; Arnold 2009). Some leading clinicians consider that the diet can be discontinued in later childhood, but others advocate lifelong dietary adjustment. There is some limited evidence that there are differences in intelligence quotient (IQ) between those who stop their low‐phenylalanine diet after childhood and those who maintain it (Poustie & Rutherford 2000).</p> <p>The low‐phenylalanine diet excludes foods high in natural protein such as meat, eggs and dairy products. Unlimited amounts of foods naturally low in phenylalanine (such as fruits and most vegetables) are allowed along with defined amounts of cereals, potatoes and other foods with moderate protein content. Calorie requirements are fulfilled by using special low‐protein foods (such as bread, rice, pasta), which are available on prescription, and patients also take a synthetic amino acid supplement. How the lifetime levels of healthcare resource use and corresponding cost of managing individuals with PKU who remain on a restricted diet, compared with those of people who stop their low‐phenylalanine diet, is unknown.</p> <p>Against this background, the aim of this study was to quantify the costs and consequences of managing PKU in the UK using patient data extracted from The Health Improvement Network (THIN) database, and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine‐restricted diet for life.</p> <hd id="AN0087564270-2">Methods</hd> <hd id="AN0087564270-3">Perspective</hd> <p>This study retrospectively estimated the costs and consequences of managing PKU sufferers in the UK over the first 36 years of their life, from the perspective of the NHS.</p> <hd id="AN0087564270-4">The Health Improvement Network database</hd> <p>The THIN database contains computerised information on 6 million anonymised patients entered by general practitioners (GPs) from 390 practices from across the UK using the Vision Practice Management Software (THIN 2008). The patient data within these 390 practices have been shown to be generalisable to the UK population (Hippisley‐Cox et al. 2008). Read codes are a coded thesaurus of clinical terms which are used by clinicians in the UK to record patient findings and procedures in health and social care IT systems (Department of Health, London 2010). They have been in use in the NHS since 1985 (Department of Health, London 2010) and have been used to code‐specific diagnoses in the THIN database. A drug dictionary based on data from the Multilex classification has been used to code drugs in the database (THIN 2008).</p> <p>The computerised information in the THIN database includes patients' demographics, details from GP consultations, specialist referrals, other clinician visits, hospital admissions, laboratory tests and prescriptions issued by GPs which are directly generated from the computer. Hence, the information contained in the THIN database reflects real clinical practice as it is based on actual patient records. Moreover, GPs are gatekeepers to healthcare in the UK and patients' entire medical history is theoretically stored in their primary care record.</p> <hd id="AN0087564270-5">Study population</hd> <p>The study population were all the patients in the THIN database who had at least one PKU Read code in their medical history and who were >15 years of age at the time of data extraction. The cut‐off age of 15 years was used as patients who stop their phenylalanine‐restricted diet generally do so after they become teenagers. Accordingly, the authors obtained the records of patients who were >15 years of age, with sufficient follow‐up data to assess the long‐term costs and outcomes of patients with PKU who do and do not remain on a phenylalanine‐restricted diet. There were no other inclusion/exclusion criteria.</p> <hd id="AN0087564270-6">Study variables</hd> <p>Information extracted from patients' records included patients' age, gender, other diagnoses and symptoms, and duration of symptoms. Community‐based and secondary care healthcare resource use over the first 36 years of the patients' life was also extracted. Missing resource use data (Table 1) were interpolated/extrapolated based on resource use in the previous or subsequent 5 years. This rule was applied, as required, up to the next available data point or up to the end of the record. Patients were stratified according to their receipt of prescriptions for an amino acid supplement and low‐protein foods, which was used as a surrogate for being on a phenylalanine‐restricted diet, and their clinical outcomes and resource use were quantified accordingly.</p> <p>1 Summary of missing data from patients' records</p> <p> <ephtml> <table><tr><th /><th align="center">Per cent of patients in each group with some missing data at different ages</th></tr><tr><th><5 years</th><th>5–10 years</th><th>11–15 years</th><th>16–20 years</th><th>21–25 years</th><th>26–30 years</th><th>31–35 years</th></tr><tr><td>Group 1</td><td>6%</td><td>6%</td><td>4%</td><td>3%</td><td>7%</td><td>9%</td><td>7%</td></tr><tr><td>Group 2</td><td>9%</td><td>6%</td><td>4%</td><td>3%</td><td>4%</td><td>8%</td><td>11%</td></tr><tr><td>Group 3</td><td>8%</td><td>8%</td><td>8%</td><td>5%</td><td>1%</td><td>1%</td><td>3%</td></tr><tr><td>Group 4</td><td>14%</td><td>11%</td><td>11%</td><td>11%</td><td>14%</td><td>16%</td><td>16%</td></tr></table> </ephtml> </p> <p>Differences in clinical outcomes between groups were tested for statistical significance using a Chi‐Square test and differences in resource use between groups were tested for statistical significance using a Mann–Whitney U‐test.</p> <hd id="AN0087564270-7">Health economic modelling</hd> <p>Using the THIN data set, a computer‐based model was constructed depicting the management of PKU patients over the first 36 years of their life. Within the model patients were stratified according to whether they started a phenylalanine‐restricted diet at <1 year of age and remained on it or discontinued or whether they had never been on a restricted diet. The model was used to estimate the incidence of co‐morbidities and associated mean age of onset, and levels of healthcare resource use over the first 36 years of a patient's life.</p> <p>This analysis was performed in 2008/09. Hence unit resource costs at 2007/08 prices (Curtis 2009; Department of Health, London 2009a) together with the cost of drugs and nutrition‐related products obtained from the Drug Tariff (2008) or the British National Formulary (2008) were applied to the resource utilisation estimates within the model in order to estimate the healthcare costs of clinical practice for PKU over the first 36 years of a patient's life, from the perspective of the UK's NHS. Discounting was not applied to the costs as the aim of the study was to estimate the cost at current prices of managing patients with PKU who do and do not remain on a phenylalanine‐restricted diet over a period of 36 years by retrospectively analysing prospectively collected healthcare resource use.</p> <p>It would have been more appropriate to estimate healthcare resource utilisation and associated costs over a patient's lifetime. However, because of the limitations in the length of patients' medical records, it was not possible to estimate resource use and corresponding costs beyond 36 years.</p> <hd id="AN0087564270-8">Sensitivity analyses</hd> <p>Sensitivity analysis is a technique in which the value of one or more model input is changed to see how the results change. Sensitivity analyses were performed to assess how the costs of managing PKU would vary by changing the resource use estimates to 50% below and 50% above the base case values.</p> <hd id="AN0087564270-9">Ethics approval</hd> <p>Ethics approval to use patients' records from the THIN database for this study was obtained from The London Research Ethics Committee, Northwick Park Hospital, Harrow, Middlesex.</p> <hd id="AN0087564270-10">Results</hd> <hd id="AN0087564270-11">Patient characteristics in the The Health Improvement Network data set</hd> <p>The THIN database contained 94 patients with at least one PKU Read code in their medical history and who were >15 years of age at the time of data extraction. The majority of the patients were born in the late 1960s or 1970s. Their mean age was 36 (95% CI: 33.9; 38.6) years and 68% were female.</p> <p>Eighty‐five per cent of all the patients (n = 80) had been put on a phenylalanine‐restricted diet when they were <1 year of age. Forty‐five per cent of these patients (n = 36) had remained on the diet (Group 1) and 55% (n = 44) had discontinued between 15 and 25 years of age. Of the 44 patients who had discontinued their phenylalanine‐restricted diet, 73% (n = 32) remained off diet (Group 2) and 12 patients had restarted the diet at a mean 30 years of age (Group 3). Nine of the patients in Group 3 were female, of whom five were aged between 22 and 30 years. The other four were aged between 35 and 45 years. Hence, some of these female patients may have restarted diet because they were planning a pregnancy. Fifteen per cent of the 94 patients (n = 14) had untreated PKU as they had never been put on a phenylalanine‐restricted diet (Group 4).</p> <p>The mean age of patients in:</p> <p>Group 1 was 34.8 (95% CI: 34.0; 35.6) years and 69% were female.</p> <p>Group 2 was 32.2 (95% CI: 30.8; 33.6) years and 69% were female.</p> <p>Group 3 was 32.9 (95% CI: 31.8; 33.9) years and 75% were female.</p> <p>Group 4 was 40.4 (95% CI: 37.6; 43.2) years and 57% were female.</p> <p>Table 2 summarises the incidence of chronic symptoms (i.e. symptoms for which patients either received continuous treatment or continued to experience) together with their mean age of onset. The incidence of neurological symptoms among patients who had stopped their phenylalanine‐restricted diet (Group 2) was double that of patients who had remained on the diet (Group 1). This was due to an observed incidence of:</p> <p>2 Incidence of chronic symptoms and mean age of onset over the first 36 years</p> <p> <ephtml> <table><tr><th>Symptoms</th><th align="center">Group 1 (n = 36)</th><th align="center">Group 2 (n = 32)</th><th align="center">Group 3 (n = 12)</th><th align="center">Group 4 (n = 14)</th></tr><tr><th>Number of patients (incidence)</th><th>Mean age of onset (years)</th><th>Number of patients (incidence)</th><th>Mean age of onset (years)</th><th>Number of patients (incidence)</th><th>Mean age of onset (years)</th><th>Number of patients (incidence)</th><th>Mean age of onset (years)</th></tr><tr><td>Cardiovascular symptoms</td><td>3</td><td>(0.08)</td><td>11.0</td><td>3</td><td>(0.09)</td><td>25.7</td><td>0</td><td>(0.00)</td><td>–</td><td>2</td><td>(0.14)</td><td>22.0</td></tr><tr><td>Headache</td><td>3</td><td>(0.08)</td><td>17.4</td><td>2</td><td>(0.06)</td><td>20.3</td><td>2</td><td>(0.17)</td><td>27.9</td><td>2</td><td>(0.14)</td><td>23.0</td></tr><tr><td>Psychiatric symptoms</td><td>3</td><td>(0.08)</td><td>21.1</td><td>3</td><td>(0.09)</td><td>22.6</td><td>2</td><td>(0.17)</td><td>28.3</td><td>2</td><td>(0.14)</td><td>22.0</td></tr><tr><td>Allergy</td><td>2</td><td>(0.06)</td><td>22.9</td><td>2</td><td>(0.06)</td><td>18.5</td><td>2</td><td>(0.17)</td><td>26.7</td><td>0</td><td>(0.00)</td><td>–</td></tr><tr><td>Neoplasia</td><td>2</td><td>(0.06)</td><td>22.5</td><td>3</td><td>(0.09)</td><td>25.9</td><td>2</td><td>(0.17)</td><td>29.0</td><td>0</td><td>(0.00)</td><td>–</td></tr><tr><td>Asthma</td><td>2</td><td>(0.06)</td><td>10.9</td><td>2</td><td>(0.06)</td><td>12.9</td><td>2</td><td>(0.17)</td><td>27.6</td><td>2</td><td>(0.14)</td><td>10.0</td></tr><tr><td>Neurological symptoms</td><td>2</td><td>(0.06)</td><td>13.2</td><td>4</td><td>(0.13)</td><td>17.0</td><td>3</td><td>(0.25)</td><td>18.3</td><td>14</td><td>(1.00)</td><td>1.0</td></tr><tr><td>Gastrointestinal symptoms</td><td>2</td><td>(0.06)</td><td>18.0</td><td>2</td><td>(0.06)</td><td>22.1</td><td>3</td><td>(0.25)</td><td>29.2</td><td>2</td><td>(0.14)</td><td>23.5</td></tr><tr><td>Arthritis and musculoskeletal symptoms</td><td>2</td><td>(0.06)</td><td>18.8</td><td>2</td><td>(0.06)</td><td>19.3</td><td>2</td><td>(0.17)</td><td>30.0</td><td>2</td><td>(0.14)</td><td>22.0</td></tr><tr><td>Dermatological symptoms</td><td>2</td><td>(0.06)</td><td>14.1</td><td>3</td><td>(0.09)</td><td>11.4</td><td>2</td><td>(0.17)</td><td>26.7</td><td>2</td><td>(0.14)</td><td>18.5</td></tr><tr><td>Otolaryngological symptoms</td><td>2</td><td>(0.06)</td><td>12.2</td><td>0</td><td>(0.00)</td><td>–</td><td>2</td><td>(0.17)</td><td>22.8</td><td>0</td><td>(0.00)</td><td>–</td></tr><tr><td>Ophthalmological symptoms</td><td>1</td><td>(0.03)</td><td>9.9</td><td>2</td><td>(0.06)</td><td>11.0</td><td>0</td><td>(0.00)</td><td>–</td><td>2</td><td>(0.14)</td><td>6.0</td></tr><tr><td>Gynaecological symptoms (estimated only from the number of female patients in the cohort)</td><td>1</td><td>(0.04)</td><td>18.0</td><td>2</td><td>(0.09)</td><td>23.1</td><td>2</td><td>(0.22)</td><td>27.3</td><td>0</td><td>(0.00)</td><td>–</td></tr></table> </ephtml> </p> <p>• Autism of 0.00 in Group 1 and 0.06 in Group 2.</p> <p>•  Epilepsy of 0.03 in Group 1 and 0.08 in Group 2.</p> <p>•  Learning disability of 0.04 in Group 1 and 0.08 in Group 2.</p> <p>•  Intellectual disability of 0.00 in Group 1 and 0.09 in Group 2.</p> <p>However, none of these differences between the Groups reached statistical significance using a Chi‐Square test, probably because of the small sample sizes.</p> <hd id="AN0087564270-12">Treatment of phenylketonuria</hd> <p>The amount of nutrition‐related prescriptions per patient varied according to whether a patient was on a phenylalanine‐restricted diet or not (Table 3). However, only 11% of patients who had remained on a phenylalanine‐restricted diet since their first year of life were found to be receiving >74% of the recommended amount of prescribed amino acid supplements. A further 6% and 28% were receiving 50–74% and 25–49% respectively and 55% were receiving <25% of the recommended amount. This is based on the number of prescriptions provided to the patients in the data set compared with the recommended number of prescribed amino acid supplements that patients would be expected to receive over their first 36 years in the experience of the clinical co‐authors.</p> <p>3 Mean number of nutrition‐related prescriptions per patient over the first 36 years</p> <p> <ephtml> <table><tr><th /><th align="center">Mean number of nutrition‐related prescriptions per patient over the first 36 years</th></tr><tr><th>Group 1 (n = 36)</th><th>Group 2 (n = 32)</th><th>Group 3 (n = 12)</th><th>Group 4 (n = 14)</th></tr><tr><td>Amino acid supplements</td><td>1194.4 (1143.3; 1245.6)</td><td>523.2 (494.7; 551.6)</td><td>484.5 (413.1; 555.9)</td><td>0.0 (0; 0)</td></tr><tr><td>Low‐protein foods</td><td>3659.7 (3426.5; 3892.9)</td><td>1138.8 (1072.5; 1205.0)</td><td>2118.0 (1979.0; 2257.0)</td><td>0.0 (0; 0)</td></tr><tr><td>Dietary supplements (such as vitamins and minerals)</td><td>1524.8 (1381.9; 1667.8)</td><td>239.6 (174.6; 304.6)</td><td>612.9 (417.3; 808.5)</td><td>185.7 (162.2; 209.2)</td></tr></table> </ephtml> </p> <p>1 95% confidence limits in parentheses.</p> <p>Figure 1 illustrates the 5‐yearly number of prescriptions for amino acid supplements and low‐protein foods per patient. Of particular note is that the number of prescriptions increased by >60% between the ages of 5 and 10 years and then plateaued in Group 1 or declined in Groups 2 and 3, but rising again in Group 3 as the patients' age exceeded 30 years.</p> <hd id="AN0087564270-13">Healthcare resource use</hd> <p>Patients' use of healthcare resources over their first 36 years of life is summarised in Table 4. Patients who remained on a phenylalanine‐restricted diet (Group 1) had approximately 12 GP visits per year, which was similar to patients in Group 3, but the frequency ranged from one visit every 2 months in those <5 years of age to two visits every 3 months in those aged 30–35 years (Fig. 2). Patients in the other two groups had approximately half that number of GP visits. Patients in Group 1 made more routine visits to their GP than patients in the other three groups. However, they made fewer non‐routine visits to their GP. In all, 20–26% of non‐routine GP visits in Groups 1, 2 and 3 were to discuss gynaecological symptoms. Additionally, 15%, 32%, 7% and 14% of non‐routine GP visits in Groups 1, 2, 3 and 4 respectively were due to dermatological symptoms. Neurological and psychiatric symptoms accounted for 22% and 29% respectively of all non‐routine GP visits in Group 4. However, these symptoms accounted for 14% or less of GP visits in the other three groups. Asthma and allergy accounted for less than 11% of all non‐routine GP visits in all four groups.</p> <p>4 Mean levels of resource use per patient over the first 36 years</p> <p> <ephtml> <table><tr><th>Resource</th><th align="center">Mean levels of resource use per patient over the first 36 years</th></tr><tr><th>Group 1 (n = 36)</th><th>Group 2 (n = 32)</th><th>Group 3 (n = 12)</th><th>Group 4 (n = 14)</th></tr><tr><td>Total GP visits</td><td>*392.1 (357.9; 426.2)</td><td>218.2 (202.1; 234.3)</td><td>316.4 (288.4; 344.4)</td><td>175.9 (160.7; 191.0)</td></tr><tr><td>Routine GP visits</td><td>**298.6 (199.6; 397.7)</td><td>117.5 (72.7; 162.3)</td><td>145.3 (87.5; 203.0)</td><td>65.5 (51.1; 79.9)</td></tr><tr><td>Non‐routine GP visits</td><td>93.4 (87.4; 99.5)</td><td>100.7 (93.3; 108.1)</td><td>171.2 (154.7; 187.6)</td><td>110.4 (95.6; 125.2)</td></tr><tr><td>Outpatient visits</td><td>*38.0 (36.0; 40.1)</td><td>27.5 (25.6; 29.4)</td><td>32.6 (29.7; 35.6)</td><td>6.2 (5.7; 6.7)</td></tr><tr><td>Hospital admissions</td><td>2.6 (1.0; 4.2)</td><td>0.8 (0.3; 1.2)</td><td>1.5 (0.8; 3.3)</td><td>2.0 (1.0; 4.1)</td></tr><tr><td>Laboratory tests</td><td>21.7 (20.4; 23.1)</td><td>20.8 (19.2; 22.4)</td><td>14.1 (12.5; 15.7)</td><td>5.1 (3.8; 6.1)</td></tr><tr><td>Diagnostic procedures</td><td>***3.7 (3.3; 4.2)</td><td>1.5 (1.3; 1.6)</td><td>2.5 (2.1; 2.8)</td><td>0.7 (0.5; 0.9)</td></tr></table> </ephtml> </p> <ulist> <item>2 95% confidence limits in parentheses.</item> <item>3 Group 1 is significantly different from Group 2; P < 0.02.</item> <item>4 Group 1 is significantly different from Group 2; P < 0.01.</item> <item>5 Group 1 is significantly different from Group 2; P < 0.05.</item> <item>6 GP, general practitioner.</item> </ulist> <p>Figure 2 illustrates that the 5‐yearly number of GP visits per patient increased substantially as the patients aged. Of particular note is that patients who discontinued their phenylalanine‐restricted diet (Groups 2 and 3) had fewer GP visits than patients who remained on diet (Group 1) and this may, to some extent, reflect the attitudes of their parents in the developmental years. Furthermore, the number of GP visits among patients in Group 3 increased markedly around the time they started developing a range of symptoms (Table 2) and restarted a phenylalanine‐restricted diet.</p> <p>Additionally, patients in Groups 1 and 3 had approximately one hospital outpatient visit per year, but those patients who remained off diet (Group 2) had fewer visits. Approximately 50% of hospital outpatient visits among patients in Groups 1, 2 and 3 were to a metabolic specialist. The other 50% of visits were accounted for by a range of specialties. Among patients in Group 4, approximately 25% of hospital outpatient visits were to an orthopaedic surgeon and 16% were to a metabolic specialist. The other 60% of visits were accounted for by a range of specialties.</p> <p>Figure 3 illustrates that the 5‐yearly number of outpatient visits per patient increased markedly as the patients aged. Of particular note is that patients who remained on their phenylalanine‐restricted diet (Group 1) had more outpatient visits than those who remained off diet (Group 2) once they were over 20 years of age. Additionally, those patients who discontinued their phenylalanine‐restricted diet and then restarted (Group 3) had more outpatient visits than patients who remained off diet (Group 2) once they were over 20 years of age.</p> <p>Patients' received prescriptions for a range of drugs over the first 36 years of their life. Of particular note is the high number of prescriptions for anti‐epileptics (n = 290 per patient) to patients in Group 4 compared to <30 anti‐epileptic prescriptions to patients in the other three groups. Similarly, a high number of prescriptions for antipsychotics were prescribed to patients in Groups 3 (n = 120 per patient) and 4 (n = 332 per patient) compared to <10 prescriptions to patients in Groups 1 and 2.</p> <p>It is also noteworthy that patients in Groups 1, 2 and 3 appeared to have their phenylalanine levels measured approximately once every 18 months to once every 2 years. However, this estimate does not include those instances when patients sent blood spots directly to the hospital for the analysis, as the results would be sent back to the patients and not the GP.</p> <hd id="AN0087564270-14">Healthcare cost of patient management</hd> <p>The mean NHS cost of managing a PKU patient over the first 36 years of their life who remained on a phenylalanine‐restricted diet was estimated to be £149 374. This compares with £54 538 for a patient who discontinued their phenylalanine‐restricted diet, £81 563 for a patient who discontinued their phenylalanine‐restricted diet and then restarted it and £21 367 for a patient who had never been on diet (Table 5). The primary reason why the cost per patient in Groups 2, 3 and 4 was less than that of patients in Group 1 is because they received substantially less nutrition‐related prescriptions. Similarly, the cost per patient in Group 2 was less than that of patients in Group 3 because they received less nutrition‐related prescriptions and had fewer GP visits. By accounting for all 94 patients in the data set, the mean NHS cost of managing a PKU sufferer over the first 36 years of their life according to actual clinical practice was estimated to be £89 000.</p> <p>5 Mean cost of resource use per patient (£ at 2007/08 prices)</p> <p> <ephtml> <table><tr><th>Resource</th><th align="center">Mean cost of resource use per patient over the first 36 years (£)</th></tr><tr><th>Group 1 (n = 36)</th><th>Group 2 (n = 32)</th><th>Group 3 (n = 12)</th><th>Group 4 (n = 14)</th></tr><tr><td>Amino acid supplements</td><td>84 396.7</td><td>(57%)</td><td>34 293.0</td><td>(63%)</td><td>46 289.0</td><td>(57%)</td><td>0.00</td><td>(0%)</td></tr><tr><td>(80 786.0; 88 014.6)</td><td>(32 425.0; 36 154.5)</td><td>(39 467.4; 53 110.5)</td><td>(0; 0)</td></tr><tr><td>Low‐protein foods</td><td>16 039.4</td><td>(11%)</td><td>4 789.5</td><td>(9%)</td><td>7 016.9</td><td>(9%)</td><td>0.00</td><td>(0%)</td></tr><tr><td>(15 017.3; 17 061.4)</td><td>(4 510.6; 5 067.9)</td><td>(6 556.4; 7 477.4)</td><td>(0; 0)</td></tr><tr><td>Dietary supplements (such as vitamins and minerals)</td><td>22 981.7</td><td>(15%)</td><td>954.8</td><td>(2%)</td><td>2 476.1</td><td>(3%)</td><td>855.6</td><td>(4%)</td></tr><tr><td>(20 827.9; 25 137.0)</td><td>(695.8; 1 213.8)</td><td>(1 685.9; 3 266.3)</td><td>(747.3; 963.9)</td></tr><tr><td>Prescribed drugs</td><td>573.5</td><td>(<1%)</td><td>1 444.6</td><td>(3%)</td><td>6 829.3</td><td>(8%)</td><td>8 611.9</td><td>(40%)</td></tr><tr><td>(257.3; 572.9)</td><td>(0; 2 988.8)</td><td>(0; 14 868.3)</td><td>(0; 17 235.0)</td></tr><tr><td>GP visits</td><td>14 114.7</td><td>(9%)</td><td>7 771.9</td><td>(14%)</td><td>11 391.0</td><td>(14%)</td><td>6 331.9</td><td>(30%)</td></tr><tr><td>(12 887.2; 15 335.0)</td><td>(7 198.4; 8 345.4)</td><td>(10 382.9; 12 399.1)</td><td>(5 784.7; 6 875.5)</td></tr><tr><td>Outpatient visits</td><td>4 598.0</td><td>(3%)</td><td>3 075.2</td><td>(6%)</td><td>3 518.5</td><td>(4%)</td><td>542.3</td><td>(3%)</td></tr><tr><td>(4 356.0; 4 852.1)</td><td>(2 826.7; 3 287.7)</td><td>(3 205.5; 3 842.3)</td><td>(498.6; 586.0)</td></tr><tr><td>Hospital admissions</td><td>6 369.3</td><td>(4%)</td><td>1 806.8</td><td>(3%)</td><td>3 646.9</td><td>(4%)</td><td>4 783.3</td><td>(22%)</td></tr><tr><td>(2 449.7; 10 288.9)</td><td>(677.6; 2 710.2)</td><td>(1 945.0; 8 023.2)</td><td>(2 391.7; 9 805.8)</td></tr><tr><td>Laboratory tests</td><td>210.3</td><td>(<1%)</td><td>143.1</td><td>(<1%)</td><td>123.7</td><td>(<1%)</td><td>40.1</td><td>(<1%)</td></tr><tr><td>(197.7; 223.9)</td><td>(132.1; 154.1)</td><td>(109.7; 137.7)</td><td>(29.9; 48.0)</td></tr><tr><td>Diagnostic procedures</td><td>90.6</td><td>(<1%)</td><td>259.1</td><td>(<1%)</td><td>271.8</td><td>(<1%)</td><td>202.1</td><td>(1%)</td></tr><tr><td>(80.8; 102.8)</td><td>(224.6; 276.4)</td><td>(228.3; 304.4)</td><td>(144.4; 259.8)</td></tr><tr><td>Total</td><td>149 374.3</td><td>(100%)</td><td>54 538.0</td><td>(100%)</td><td>81 563.1</td><td>(100%)</td><td>21 367.2</td><td>(100%)</td></tr><tr><td>(136 860.0; 161 588.6)</td><td>(48 726.7; 60 198.7)</td><td>(63 581.1; 103 429.1)</td><td>(9 596.5; 35 773.9)</td></tr></table> </ephtml> </p> <ulist> <item>7 95% confidence limits and per cent of total cost in parentheses.</item> <item>8 GP, general practitioner.</item> </ulist> <p>Amino acid supplements were the primary cost driver in Groups 1, 2 and 3 accounting for 57%, 63% and 57% of the 36‐yearly cost respectively. Prescribed drugs were the primary cost driver in Group 4 accounting for 40% of the 36‐yearly cost, GP visits were the secondary cost driver in all four groups accounting for a further 9–30% of the 36‐yearly cost.</p> <hd id="AN0087564270-15">Sensitivity analyses and budget impact</hd> <p>Deterministic sensitivity analyses (Table 6) demonstrated that the model is relatively robust and that the only parameter that could potentially change the results was the number of nutrition‐related prescriptions. Changing the amount of resource use per patient in each group to 50% below and 50% above the base case values resulted in a variance of <10% in the total mean cost of resource use per patient, with the exception of nutrition‐related prescriptions. Changing the number of prescribed amino acid supplements per patient to 50% below and 50% above the base case value in Groups 1, 2 and 3 resulted in a variance of ∼30% in the total mean cost of resource use per patient.</p> <p>6 Sensitivity analyses</p> <p> <ephtml> <table><tr><th>Resource</th><th align="center">Range in the total mean cost of resource use per patient when the amount of individual resource use is changed to 50% below and 50% above the base case value in:</th></tr><tr><th>Group 1 (£)</th><th>Group 2 (£)</th><th>Group 3 (£)</th><th>Group 4 (£)</th></tr><tr><td>Routine GP visits</td><td>143 996–154 745</td><td>52 505–56 735</td><td>78 951–84 182</td><td>20 188–22 546</td></tr><tr><td>Non‐routine GP visits</td><td>147 689–151 051</td><td>52 808–56 433</td><td>78 485–84 648</td><td>19 380–23 354</td></tr><tr><td>Outpatient visits</td><td>147 072–151 670</td><td>53 083–56 158</td><td>79 808–83 326</td><td>21 096–21 638</td></tr><tr><td>Hospital admissions</td><td>146 186–152 555</td><td>53 717–55 524</td><td>79 743–83 390</td><td>18 976–23 759</td></tr><tr><td>Laboratory tests</td><td>149 265–149 476</td><td>54 549–54 692</td><td>81 505–81 629</td><td>21 347–21 387</td></tr><tr><td>Prescribed drugs</td><td>149 084–149 657</td><td>53 898–55 343</td><td>78 152–84 981</td><td>17 061–25 673</td></tr><tr><td>Prescribed amino acid supplements</td><td>107 172–191 569</td><td>37 474–71 767</td><td>58 422–104 711</td><td>21 367–21 367</td></tr><tr><td>Prescribed low‐protein foods</td><td>141 351–157 390</td><td>52 226–57 016</td><td>78 058–85 075</td><td>21 367–21 367</td></tr><tr><td>Prescribed dietary supplements</td><td>137 880–160 861</td><td>54 143–55 098</td><td>80 329–82 805</td><td>20 939–21 795</td></tr></table> </ephtml> </p> <p>9 GP, general practitioner.</p> <p>The incidence of PKU in the UK has been estimated at one in 10 000 live births (Hardelid et al. 2008). The annual number of live births in the UK is 670 000 babies (ONS 2009). Hence, there are approximately 67 new PKU sufferers per annum. Based on the treatment algorithms of the patients in Group 1, a current annual cohort of 67 PKU sufferers is expected to cost the NHS an undiscounted sum of £23 million over the next 36 years, providing they receive and remain on an optimum amount of phenylalanine‐restricted diet over this period (i.e. ∼£9500 per patient per year). However, this estimate should be viewed with caution as the temporal changes in patient management over the last 36 years could potentially confound any predictions.</p> <p>There are an estimated 2500 PKU sufferers currently in the UK. Based on the treatment algorithms of patients in Group 1, the current NHS cost to treat them with an optimum phenylalanine‐restricted diet was estimated to be £24 million per year (i.e. ∼£9500 × 2500), which represents <0.1% of the total annual NHS budget [which was £108 billion at 2008/09 (Department of Health, London 2009b)].</p> <hd id="AN0087564270-16">Discussion</hd> <p>This study is one of the few health economic studies in this therapeutic area and to the authors' knowledge, this is the first time that clinical outcomes and resource use have been compared between patients who have and have not remained on a phenylalanine‐restricted diet. The advantages of using the THIN database is that the treatment patterns observed in this study reflect actual clinical practice. However, this naturalistic approach does have its limitations, one of which is that cause and effect cannot be ascertained. Additionally, patients were not randomised to the treatment they received and resource use, while collected prospectively, was analysed retrospectively. Nevertheless, all eligible patients in the THIN database have been included in the analysis, enabling an assessment of the treatment patterns, clinical outcomes and healthcare resource use attributable to managing a cohort of PKU patients in actual clinical practice.</p> <p>The PKU patients in the THIN data set had a mean 36 years of history in their records, with some of the older patients having up to 67 years of data. The results have therefore been truncated at 36 years and excluded the costs and consequences of managing patients beyond this period. Hence, this study represents an assessment of the costs and outcomes attributable to managing PKU sufferers in clinical practice in the UK over the first 36 years of their life. The sample size in our study is small in absolute terms, reflecting the low incidence of the disease, although the incidence of PKU in the THIN database was concordant with the incidence in the UK. Moreover, there were gaps in the records of some of the patients, particularly in Group 4 and therefore the findings from this Group should be viewed with caution. However, sensitivity analyses showed that if the margin of error in any of the resource use estimates was as high as 50%, the variance in the total cost per patient would be within 10% of the calculated value. Moreover, it was not possible to disentangle this study's observations from any cohort, temporal or other effects that may have confounded the results, due in part to the small sample size and the study period of 36 years. Nevertheless, this remains one of the largest cohort studies on PKU ever undertaken with the longest period of follow up.</p> <p>In a quality‐of‐life study among 53 adult patients in Poland who had stopped taking a restricted diet, 17% experienced severe distress, 28% moderate distress and 55% positive well‐being. Returning to a restricted diet increased their quality of life, but the high cost of low‐protein products and poor knowledge regarding a restricted diet contributed to their failure in maintaining the diet (Bik‐Multanowski et al. 2008). Our study was unable to consider the quality of life of the patients in the THIN data set because it was a retrospective analysis. Other studies have reported that adults who relax their restricted diet risk developing neurological impairments, such as lack of concentration, poor performance, moodiness, poor spatial ability, defective motor coordination and hyperactivity (Hunt et al. 1985; Villasana et al. 1989; Thompson et al. 1990; MRC Working Party on Phenylketonuria 1993a; Cerone et al. 1999; NIH Consensus Statement 2000) as well as changes in subcortical white matter (Bick et al. 1991; Thompson et al. 1991; NIH Consensus Statement 2000). Some of our observations are concordant with these studies. Nevertheless, other studies have reported that early diagnosed patients who were well treated and of good intellectual outcome do not exhibit neurological deterioration after stopping diet (Brenton & Pietz 2000).</p> <p>This study demonstrated that GPs play an instrumental role in PKU management, with patients visiting their general practice at least once every 2 months. The actual frequency of GP visits varied according to whether a patient remained on a phenylalanine‐restricted diet. Conversely, most patients visited a hospital consultant about once a year, although this frequency was marginally less among patients not on a phenylalanine‐restricted diet. Surprisingly, patients appeared to have their phenylalanine levels measured less frequently than once a year. Notwithstanding this, the frequency of clinician visits to both GPs and hospital physicians increased as the patients aged. The reasons for this are unclear, but may be due to increasing morbidity as patients aged. Additionally, it is important to note that just because a group of patients use fewer resources (i.e. Groups 2 and 4), it does not necessarily imply that those groups received either the preferred or optimum treatment.</p> <p>The most surprising finding of the study was that 89% of patients who remained on a restricted diet for the first 36 years of life appeared to receive less than the recommended optimum amount of prescribed amino acid supplements. The reasons for this are unclear, but may warrant the need for clear guidelines on the management of PKU focused towards primary care, as GPs are predominantly responsible for prescribing amino acid supplements to PKU patients. Furthermore, it is possible that the incidence of symptoms observed among patients in Group 1 (with a mean age of onset ranging from 10 to 23 years) is a reflection of them having received inadequate amounts of phenylalanine‐restricted nutrition rather than the condition of PKU per se. It is unknown whether the incidence of symptoms observed in this Group would have been lower had they received adequate amounts of phenylalanine‐restricted nutrition.</p> <p>The study's results may be confounded by certain other limitations within the model. The THIN database may have under‐recorded use of some resources outside the GP's surgery, such as home visits made by GPs, nurses and social workers. The analysis also excluded hospital‐based prescribing, but this should have minimal impact on the results as most prescribing is undertaken by GPs in the community. The analysis only considered NHS resource use and corresponding costs for an ‘average patient’ stratified by their use of a phenylalanine‐restricted diet and no attempt has been made to stratify costs according to patients' co‐morbidities, disease severity and other disease‐related factors. Also excluded are the costs incurred by patients and their parents and indirect costs incurred by society as a result of patients and their parents taking time off work. The analysis excluded changes in quality of life and improvements in general well‐being of sufferers and their parents. Also excluded are changes in patients' behaviour. Consequently this study may have underestimated the burden that PKU imposes on society as a whole.</p> <p>In summary, the study suggests that the majority of patients who remained on a phenylalanine‐restricted diet for the first 36 years of life received less than optimum amounts of prescribed amino acid supplements. Also, while the observed differences in the incidence of symptoms between the different groups were not statistically significant, they may be clinically meaningful and should therefore be the target for further research, such as a longitudinal comparative study between patients who have and have not remained on a phenylalanine‐restricted diet. This may help clarify the uncertainties concerning the consequences of stopping diet. Notwithstanding this, the total NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long‐term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet.</p> <hd id="AN0087564270-17">Acknowledgements</hd> <p>This study was sponsored by SHS International Ltd, Liverpool, UK, manufacturers of the range of Anamix and Lophlex products designed for use in the dietary management of PKU. However, the authors have no other conflicts of interest that are directly relevant to the content of this manuscript. In particular, SHS International Ltd had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. The authors have no other financial and personal relationships with other people or organisations that could inappropriately influence (bias) this study.</p> <ref id="AN0087564270-18"> <title>References</title> <blist> <bibl id="bib1" type="bt">1</bibl> <bibtext>Arnold G. ( 2009 ) Phenylketonuria. 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Available at: <ulink href="http://consensus.nih.gov/2000/2000Phenylketonuria113html.htm">http://consensus.nih.gov/2000/2000Phenylketonuria113html.htm</ulink> (retrieved February 2010). </bibtext> </blist> <blist> <bibl id="bib22" type="bt">22</bibl> <bibtext>Office for National Statistics (ONS), London ( 2009 ) Available at: <ulink href="http://www.ons.gov.uk/ons/index.html">http://www.ons.gov.uk/ons/index.html</ulink> (retrieved February 2010). </bibtext> </blist> <blist> <bibl id="bib23" type="bt">23</bibl> <bibtext>Potocnik U. & Widhalm K. ( 1994 ) Long‐term follow‐up of children with classical phenylketonuria after diet discontinuation: a review. Journal of the American College of Nutrition 13, 232 – 6. </bibtext> </blist> <blist> <bibl id="bib24" type="bt">24</bibl> <bibtext>Poustie V. J. & Rutherford P. ( 2000 ) Dietary interventions for phenylketonuria. Cochrane Database of Systematic Reviews ( 2 ), CD001304. </bibtext> </blist> <blist> <bibl id="bib25" type="bt">25</bibl> <bibtext>The Health Improvement Network (THIN) Database ( 2008 ) EPIC London. </bibtext> </blist> <blist> <bibl id="bib26" type="bt">26</bibl> <bibtext>Thompson A. J., Smith I., Brenton D., Youl B. D., Rylance G., Davidson D. C. et al. ( 1990 ) Neurological deterioration in young adults with phenylketonuria. Lancet 336, 602 – 5. </bibtext> </blist> <blist> <bibl id="bib27" type="bt">27</bibl> <bibtext>Thompson A. J., Smith I., Kendall B. E., Youl B. D. & Brenton D. ( 1991 ) Magnetic resonance imaging changes in early treated patients with phenylketonuria. Lancet 337, 1224. </bibtext> </blist> <blist> <bibl id="bib28" type="bt">28</bibl> <bibtext>Villasana D., Butler I. J., Williams J. C. & Roongta S. M. ( 1989 ) Neurological deterioration in adult phenylketonuria. Journal of Inherited Metabolic Disease 12, 451 – 7. </bibtext> </blist> <blist> <bibl id="bib29" type="bt">29</bibl> <bibtext>Williams R. A., Mamotte C. D. & Burnett J. R. ( 2008 ) Phenylketonuria: an inborn error of phenylalanine metabolism. The Clinical Biochemist. Reviews 29, 31 – 41. </bibtext> </blist> </ref> <p>Graph: 1 Mean number of prescriptions for amino acid supplements and low‐protein foods per patient over the first 36 years of life in each period.</p> <p>Graph: image%5fn/jir1568%5ff1.gif</p> <p>Graph: 2 Mean number of general practitioner (GP) visits per patient over the first 36 years of life in each period.</p> <p>Graph: image%5fn/jir1568%5ff2.gif</p> <p>Graph: 3 Mean number of outpatient visits per patient over the first 36 years of life in each period.</p> <p>Graph: image%5fn/jir1568%5ff3.gif</p> <aug> <p>By J. F. Guest; J. J. Bai; R. R. Taylor; E. Sladkevicius; P. J. Lee and R. H. Lachmann</p> </aug>
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  Data: Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet
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  Data: <searchLink fieldCode="AR" term="%22Guest%2C+J%2E+F%2E%22">Guest, J. F.</searchLink><br /><searchLink fieldCode="AR" term="%22Bai%2C+J%2E+J%2E%22">Bai, J. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Taylor%2C+R%2E+R%2E%22">Taylor, R. R.</searchLink><br /><searchLink fieldCode="AR" term="%22Sladkevicius%2C+E%2E%22">Sladkevicius, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Lee%2C+P%2E+J%2E%22">Lee, P. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Lachmann%2C+R%2E+H%2E%22">Lachmann, R. H.</searchLink>
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  Data: <searchLink fieldCode="SO" term="%22Journal+of+Intellectual+Disability+Research%22"><i>Journal of Intellectual Disability Research</i></searchLink>. Jun 2013 57(6):567-579.
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  Data: Wiley-Blackwell. 350 Main Street, Malden, MA 02148. Tel: 800-835-6770; Tel: 781-388-8598; Fax: 781-388-8232; e-mail: cs-journals@wiley.com; Web site: http://www.wiley.com/WileyCDA/
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  Data: 13
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  Data: 2013
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  Data: Journal Articles<br />Reports - Research
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  Data: <searchLink fieldCode="DE" term="%22Foreign+Countries%22">Foreign Countries</searchLink><br /><searchLink fieldCode="DE" term="%22Diseases%22">Diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolism%22">Metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Dietetics%22">Dietetics</searchLink><br /><searchLink fieldCode="DE" term="%22Comorbidity%22">Comorbidity</searchLink><br /><searchLink fieldCode="DE" term="%22Access+to+Health+Care%22">Access to Health Care</searchLink><br /><searchLink fieldCode="DE" term="%22Costs%22">Costs</searchLink><br /><searchLink fieldCode="DE" term="%22Longitudinal+Studies%22">Longitudinal Studies</searchLink><br /><searchLink fieldCode="DE" term="%22Patients%22">Patients</searchLink><br /><searchLink fieldCode="DE" term="%22Health+Services%22">Health Services</searchLink><br /><searchLink fieldCode="DE" term="%22Databases%22">Databases</searchLink><br /><searchLink fieldCode="DE" term="%22Symptoms+%28Individual+Disorders%29%22">Symptoms (Individual Disorders)</searchLink><br /><searchLink fieldCode="DE" term="%22Disabilities%22">Disabilities</searchLink><br /><searchLink fieldCode="DE" term="%22Nutrition%22">Nutrition</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Therapy%22">Drug Therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Hospitals%22">Hospitals</searchLink>
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  Label: Geographic Terms
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  Data: <searchLink fieldCode="DE" term="%22United+Kingdom%22">United Kingdom</searchLink>
– Name: DOI
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  Data: 10.1111/j.1365-2788.2012.01568.x
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  Data: 0964-2633
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: To quantify the costs and consequences of managing phenylketonuria (PKU) in the UK and to estimate the potential implications to the UK's National Health Service (NHS) of keeping patients on a phenylalanine-restricted diet for life. Methods: A computer-based model was constructed depicting the management of PKU patients over the first 36 years of their life, derived from patients suffering from this metabolic disorder in The Health Improvement Network database (a nationally representative database of patients registered with general practitioners in the UK). The model was used to estimate the incidence of co-morbidities and the levels of healthcare resource use and corresponding costs over the 36 years. Results: Patients who remained on a phenylalanine-restricted diet accounted for 38% of the cohort. Forty-seven per cent of patients discontinued their phenylalanine-restricted diet between 15 and 25 years of age. Of these, 73% remained off diet and 27% restarted a restricted diet at a mean 30 years of age. Fifteen per cent of the cohort had untreated PKU. Eleven per cent of patients who remained on a phenylalanine-restricted diet for 36 years received the optimum amount of prescribed amino acid supplements. Patients had a mean 12 general practitioner visits per year and one hospital outpatient visit annually, but phenylalanine levels were only measured once every 18 to 24 months. The mean NHS cost (at 2007/08 prices) of managing a PKU sufferer over the first 36 years of their life was estimated to range between 21 000 pounds and 149 000 pounds, depending on the amount of prescribed nutrition they received. Conclusion: The findings suggest that the majority of patients with PKU were under-treated. The NHS cost of patient management should not be an obstacle to encouraging patients to remain on a restricted diet until further information becomes available about the long-term clinical impact of stopping such a diet. Nevertheless, patients require counselling and managed follow up regardless of the choices they make about their diet. (Contains 6 tables and 3 figures.)
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  Data: 2014
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  Data: EJ1013026
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        Value: 10.1111/j.1365-2788.2012.01568.x
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      – Text: English
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        PageCount: 13
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      – SubjectFull: Foreign Countries
        Type: general
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      – TitleFull: Costs and Outcomes over 36 Years of Patients with Phenylketonuria Who Do and Do Not Remain on a Phenylalanine-Restricted Diet
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