Inborn errors of the pyruvate dehydrogenase complex (PDC) are associated with lactic acidosis, neuroanatomic defects, developmental delay, and early death. PDC deficiency is a clinically heterogeneous disorder, with most mutations located in the coding region of the X-linked alpha subunit of the first catalytic component, pyruvate dehydrogenase (E1). Treatment of E1 deficiency hs included cofactor replacement, activation of PDC with dichloroacetate, and ketogenic diets. In this report, we describe the outcome of ketogenic diet treatment in seven boys with E1 deficiency. These patients were divided into two groups based on their mutations (R349H, three patients; and R234G, four patients, two sibling pairs). All seven patients received ketogenic diets with varying degrees of carbohydrate restriction. Clinical outcome was compared within each group and between siblings as related to the intensity and duration of dietary intervention. Subjects who either had the diet initiated earlier in life or who were placed on greater carbohydrate restriction had increased longevity and improved mental development. Based on the improved outcomes of patients with identical mutations, it appears that a nearly carbohydrate-free diet initiated shortly after birth may be useful in the treatment of E1 deficiency.

OBJECTIVEThe American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes.RESEARCH DESIGN AND METHODSAfter development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach α and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen.RESULTSPCQ mean score was 87 ± 9.7% (range 42–98%). Cronbach α was 0.88, and correlation of split halves was 0.59 (P < 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = −0.29, P = 0.01) and expert assessments (r = 0.56, P < 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003).CONCLUSIONSThe PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ.

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Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

The aim of the present study was to examine the impact of an antimicrobial prescribing protocol on clinical and economic outcome measures in hospitalized patients with community-acquired lower respiratory tract infection (LRTI). The study was performed as a prospective controlled clinical trial within the medical wards at Antrim Area Hospital, Northern Ireland. Data were collected on all hospitalized adult patients with a primary diagnosis of LRTI during the period December 1994 to February 1995 (normal hospital practice; control group; n = 112). After an LRTI management protocol (medical, microbiological and pharmacy staff) had been developed, all hospitalized adult patients with a primary diagnosis of LRTI over the period December 1995 to February 1996 formed the intervention group (treated according to the protocol; n = 115). The results showed a statistically significant impact of the protocol in terms of clinical and economic outcome measures. Patients treated using the algorithmic prescribing protocol had significant reductions in length of hospital stay (geometric mean 4.5 versus 9.2 days), iv drug administration (34.8% versus 61.6%), duration of iv therapy (geometric mean 2.1 versus 5.7 days) and treatment failures (7.8% versus 31.3%). Healthcare costs were also significantly reduced. The use of the protocol was a major factor in streamlining the prescribing of antimicrobial therapy for community-acquired LRTI and led to more cost-effective patient management.

A situational analysis was conducted to evaluate challenges with the treatment regimen (a low protein diet and special supplemental formula) for children and adolescents with phenylketonuria (PKU) and their caregivers. A semistructured interview was administered to 19 caregivers and 11 children with PKU to describe formula and dietary problems and their frequency, difficulty, and affective intensity. Information was also gathered on attempted solutions to problems and their perceived effectiveness. Caregivers who rated dietary problems as less frequent, difficult, and emotionally upsetting and strategies as more effective for solving problems had children with significantly lower phenylalanine (Phe) levels, a biological indicator of adherence (i.e., better adherence; all p values <.05). Caregivers who reported using strategies coded as representing an authoritarian parenting style to solve dietary problems were significantly more likely to have lower household incomes and older children with higher Phe levels than were those who did not report such strategies (all p values <.05).

It is regrettable that while the recognised complications of ureterosigmoid anastomosis - recurrent urinary tract infection, and acidosis- can be avoided and obstructive uropathy can be recognised early and so treated, the operation frequently condemns the patient to a restricted life with an unpleasant ritual of bowel frequency and incontinence. It seems that the lack of awareness of this bizarre life-style and the occasional true successes have allowed the operation to remain in use. Our experience confirms the unpredictability of the end result of ureterosigmoid anastomosis and suggests that the operation should be largely abandoned, in favour of the conduit type procedure.

1. After a fixed weight-related dose given intravenously, plasma diazepam concentrations were significantly lower in 11 cirrhotic patients than in controls matched for age and sex, in the 4 h after diazepam administration but not thereafter. 2. When measured at a single fixed time point, a greater proportion of the drug was in the unbound from in the plasma of cirrhotic patients, but non-bound diazepam concentrations were not significantly different in the two groups. 3. Several psychomotor tests showed that cirrhotic patients, although having significantly impaired liver function, did not as a group have increased sensitivity to diazepam compared with their matched controls. 4. Only those cirrhotic patients who at the time of drug administration had impaired cerebral function, as judged by baseline performance of psychomotor tests, showed increased sensitivity to the effects of intravenous diazepam. 5. Psychomotor tests, particularly the Reitan trail test, seem more useful than tests of liver function or drug metabolism for identifying those patients with liver cirrhosis at risk of excessive sedation after diazepam administration.