Identification of patients with Fabry disease using routine pathology results: PATHFINDER (eGFR) study.

AIMS: Lysosomal α-galactosidase A deficiency (Fabry disease (FD)) was considered an X-linked recessive disorder but is now viewed as a variable penetrance dominant trait. The prevalence of FD is 1 in 40 000-117 000 but the ascertainment of late-onset cases and degree of female penetrance makes this unclear. Its prevalence in the general population, especially in patients with abnormal renal function is unclear. This study attempted to identify the prevalence of FD in patients with abnormal renal function results from laboratory databases. METHODS: Electronic laboratory databases were interrogated to identify from clinical biochemistry records patients with a phenotype of reduced estimated glomerular filtration rate categorised by age on one occasion or more over a 3-year time interval. Patients were recalled and a dried blood spot sample was collected for the determination of α-galactosidase A activity by fluorimetric enzyme assay in men and mass spectrometry assays of α-galactosidase A and lyso-globotriaosylceramide (lyso-GL-3) concentrations in women. RESULTS: Samples were obtained from 1084 patients identified with reduced renal function. No cases of FD were identified in 505 men. From 579 women, one subject with reduced α-galactosidase activity (1.5 µmol/L/h) and increased Lyso-GL-3 (5.5 ng/mL) was identified and shown to be heterozygous for a likely FD pathogenic variant (GLA c.898C>T; p.L300F; Leu300Phe). It was later confirmed that she was a relative of a known affected patient. CONCLUSIONS: Pathology databases hold routine information that can be used to identify patients with inherited errors of metabolism. Biochemical screening using reduced eGFR alone has a low yield for unidentified cases of Fabry Disease.

Identification of patients with Pompé disease using routine pathology results: PATHFINDER (creatine kinase) study.

AIMS: Adult-onset inherited errors of metabolism can be difficult to diagnose. Some cases of potentially treatable myopathy are caused by autosomal recessive acid α-1,4 glucosidase (acid maltase) deficiency (Pompé disease). This study investigated whether screening of asymptomatic patients with elevated creatine kinase (CK) could improve detection of Pompé disease. METHODS: Pathology databases in six hospitals were used to identify patients with elevated CK results (>2× upper limit of normal). Patients were recalled for measurement of acid α-1,4 glucosidase activity in dried blood spot samples. RESULTS: Samples were obtained from 812 patients with elevated CK. Low α-glucosidase activity was found in 13 patients (1.6%). Patients with neutropaenia (n=4) or who declined further testing (n=1) were excluded. Confirmation plasma specimens were obtained from eight individuals (1%) for a white cell lysosomal enzyme panel, and three (0.4%) were confirmed to have low α-1,4-glucosidase activity. One patient was identified as a heterozygous carrier of an acid α-1,4 glucosidase c.-32-13 G>T mutation. Screening also identified one patient who was found to have undiagnosed Fabry disease and one patient with McArdle's disease. One patient later presented with Pompé's after an acute illness. Including the latent case, the frequency of cases at 0.12% was lower than the 2.5% found in studies of patients with raised CK from neurology clinics (p<0.001). CONCLUSIONS: Screening pathology databases for elevated CK may identify patients with inherited metabolic errors affecting muscle metabolism. However, the frequency of Pompé's disease identified from laboratory populations was less than that in patients referred for neurological investigation.

Progressive Mobility Protocol Reduces Venous Thromboembolism Rate in Trauma Intensive Care Patients: A Quality Improvement Project.

The intensive care unit (ICU) trauma population is at high risk for complications associated with immobility. The purpose of this project was to compare ICU trauma patient outcomes before and after implementation of a structured progressive mobility (PM) protocol. Outcomes included hospital and ICU stays, ventilator days, falls, respiratory failure, pneumonia, or venous thromboembolism (VTE). In the preintervention cohort, physical therapy (PT) consults were placed 53% of the time. This rose to more than 90% during the postintervention period. PT consults seen within 24 hr rose from a baseline 23% pre- to 74%-94% in the 2 highest compliance postintervention months. On average, 40% of patients were daily determined to be too unstable for mobility per protocol guidelines-most often owing to elevated intracranial pressure. During PM sessions, there were no adverse events (i.e., extubation, hypoxia, fall). There were no significant differences in clinical outcomes between the 2 cohorts regarding hospital and ICU stays, average ventilator days, mortality, falls, respiratory failure, or pneumonia overall or within ventilated patients specifically. There was, however, a difference in the incidence of VTE between the preintervention cohort (21%) and postintervention cohort (7.5%) (p = .0004). A PM protocol for ICU trauma patients is safe and may reduce patient deconditioning and VTE complications in this high-risk population. Multidisciplinary commitment, daily protocol reinforcement, and active engagement of patients/families are the cornerstones to success in this ICU PM program.

The first structural and spectroscopic characterisation of a ring-opened form of a 2H-naphtho[1,2-b]pyran: a novel photomerocyanine.

Heating 4-methoxy-1-naphthol with a 1,1-diarylprop-2-yn-1-ol gave the 2,2-diaryl-6-methoxy-2H-naphtho[1,2-b]pyran together with the novel merocyanine, (E)-2-[3',3'-bis(aryl)allylidene]-4-methoxynaphthalen-1(2H)-one. Brief UV-irradiation of the pyran favoured the formation of the (Z)-merocyanine with longer irradiation and/or acidic conditions favouring the (E)-isomer.

A practical method for monitoring general practice mortality in the UK: findings from a pilot study in a health board of Northern Ireland.

BACKGROUND: The Baker report into Dr Harold Shipman's murders recommended monitoring mortality in general practice, but there is currently no practical method available to implement this. AIM: To monitor mortality rates in response to the Baker report and to use the data to improve quality of care. DESIGN OF STUDY: Prospective mortality monitoring study. SETTING: Eastern Health and Social Services Board, Northern Ireland. METHOD: Linked quarterly mortality data from 1994-2001 were compiled for 114 general practices in Eastern Health and Social Services Board in Northern Ireland. Cross-sectional control charts compared crude and adjusted mortality rates across all the practices. Longitudinal control charts analysed quarterly mortality rates over 28 quarters within each practice. Practices were sent their own control charts and invited to feedback workshops. Special cause variation in mortality was investigated as follows: checks on data, case-mix, practice structures, processes of care and finally individual carers. RESULTS: Age, sex and deprivation adjusted cross-sectional control charts identified 18 practices as showing special cause variation in their mortality (11 high and 7 low). Assignable causes were found for all high special cause practices: large numbers of nursing home patients (six practices), very high levels of deprivation and high morbidity not captured by our case-mix adjustment (five practices). For three of seven low special cause practices, case-mix adjustment underestimated affluence and overestimated morbidity levels. Feedback indicated widespread support for the principle of monitoring, but concerns about the public disclosure of mortality data. CONCLUSIONS: We have successfully developed and piloted a general practice mortality monitoring system with the support and participation of local stakeholders. This used control charts for analysis and followed a scientific strategy for investigating special cause variation.