Costs and outcomes over 36 years of patients with phenylketonuria who do and do not remain on a phenylalanine-restricted diet.

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. METHOD: 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.

Long-term needs of adult patients with organic acidaemias: outcome and prognostic factors.

BACKGROUND: With improvements in the treatment of children with organic acidaemias (OA), the number surviving to adulthood is increasing. To plan appropriate services for their care it is important to know what their needs are. OBJECTIVE: To describe the clinical and social problems affecting adult patients with OA. PATIENTS AND METHODS: We reviewed the medical records of 15 adult patients diagnosed with OA. Social attainment (housing, schooling and occupation) was analysed. Nutritional status was evaluated by body mass index (BMI) and laboratory studies. Neurological and visceral complications were noted. Cognitive outcome was evaluated by psychometric testing and/or educational attainment. RESULTS: Seven had methylmalonic acidaemia (MMA), 4 isovaleric acidaemia (IVA) and 4 propionic acidaemia (PA). Ten were female, and median age was 23.5 years (range 18-48). All but three had late-onset disease. Two patients became pregnant during follow up. Four patients had obtained university degrees and were working. Three-quarters of the patients required some kind of social support. All had a good nutritional status. Height was normal in IVA and 3 PA patients. Osteoporosis was present in 2 out of 8 patients assessed. A variety of neurocognitive or visceral complications were seen in two-thirds of the patients. Metabolic decompensations were unusual. CONCLUSIONS: The approach to adult patients with OA has to be multidisciplinary, with the clinician and dietician as the core of the team, but with the collaboration of clinical nurses specialists, social workers and other specialist services and the support of a biochemical and molecular laboratory.

Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring.

More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.

Homocysteine and cysteine - albumin binding in homocystinuria: assessment of cysteine status and implications for glutathione synthesis?

Measurement of plasma total cysteine rather than free dimeric cystine gives a better indication of cysteine status in homocystinuric patients. This is the result of displacement of cysteine from albumin by homocysteine and is related to the plasma homocysteine concentration. In control subjects the free/bound cyst(e)ine ratio was independent of albumin and total cysteine concentrations. In homocystinuric (HCU) patients both free and total cyst(e)ine values differed significantly from control values (P < 0.001) but whilst free cystine considerably overlapped control values the total cysteine concentrations were almost invariably lower. The possible consequences of this on glutathione synthesis was explored by assay of plasma total glutathione but no evidence for glutathione deficiency was found. Measurement of total cysteine, rather than free cystine, provides a better indication of cysteine status in HCU.

Correlates of depression in older Latinos.

OBJECTIVE: To report the rates of depressive disorders--i.e., major and subthreshold depression--as well as the correlates of depression in a sample of older Latino primary care consumers. The study addresses the gap in the literature concerning depression and older Latinos residing in the U.S. DATA SOURCES AND STUDY SETTING: Data were collected from 150 Latino primary care consumers (50+ years-old) in Los Angeles County. Depression was measured using the depression module of the PRIME-MD Patient Health Questionnaire. Demographic, stress-related, health, and social integration data were also collected. STUDY DESIGN: A cross sectional design was employed vis-à-vis face-to-face interviews of respondents at the clinic sites or in their homes. Descriptive analyses and logistic regression modeling were used to describe the sample and to examine the correlates of depression. PRINCIPLE FINDINGS: Rates of depression indicate that 24.1% of the sample reported symptoms sufficient to meet the criteria for a PHQ depression diagnosis. Only social functioning and income were associated with the presence of a depressive disorder. Interference with social activities with family and friends as a result of physical and emotional problems was associated with a 1.86-fold increase risk of being depressed. CONCLUSIONS: Although most of the cases were classified as subthreshold, prior work has shown that subthreshold depression can be clinically significant and debilitating. Using brief screening instruments such as the PHQ, practitioners can identify cases needing further assessment and treatment.

Unemployment and health: the healthcare system's role.

Experts from the South Western Sydney Area Health Service and the University of New South Wales say there are few reports of healthcare interventions to address the impact of unemployment on health. They outline possible strategies, which include providing accessible and appropriate healthcare; developing the healthcare system's capacity to deal with the health problems of unemployed people; collaborating with other agencies and sectors working on this issue; acting as an advocate for unemployed people; undertaking research; and providing training, work experience and employment opportunities within the healthcare system. Long term solutions lie in increasing employment and training opportunities. Nevertheless, there is a clear role for the healthcare system in reducing the health impacts of unemployment and ensuring that poor health does not act as a barrier to returning to work.