Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression.

BACKGROUND: Enzyme replacement therapy (ERT) slows disease progression of Fabry disease (FD), especially when initiated before the onset of irreversible organ damage. However, with the clinically asymptomatic progression of renal, cardiac and cerebral disease manifestations spanning decades, optimal timing of ERT initiation remains unclear. METHODS: In this cross-sectional retrospective study, seven male FD patients with a classical disease phenotype (cFD) who started treatment with agalsidase-beta in childhood were evaluated after 10 years of treatment (median age at evaluation 24 years, range 14-26). Cardiac imaging (echocardiography and MRI), electrophysiological and biochemical data of these patients were compared to those of untreated male cFD patients (n = 23, median age 22 years, range 13-27). RESULTS: Albuminuria was less common and less severe in treated patients (albumin to creatinine ratio, ACR 0-8.8 mg/mmol, median 0.4) compared to untreated patients (ACR 0-248 mg/mmol, median 3.7, p = 0.02). The treated group had a lower left ventricular mass, measured using echocardiography (median 80 g/m2 versus 94 g/m2, p = 0.02) and MRI (median 53 g/m2 versus 68 g/m2, p = 0.02). Myocardial fibrosis was absent in all included patients. eGFR was normal in all treated patients whereas 7/23 (30%) of untreated patients had abnormal eGFR. Cerebral manifestations did not differ. CONCLUSIONS: Start of treatment with ERT before age 16, in male cFD patients is associated with reduced occurrence of renal and cardiac manifestations of FD, as assessed by intermediate endpoints. Confirmation that this approach delays or even prevents renal failure and cardiac events requires another decade of follow-up.

Success of community-based directly observed anti-tuberculosis treatment in Mongolia.

BACKGROUND: Many countries restrict access to directly observed therapy (DOT) for tuberculosis (TB) to government health facilities. More innovative approaches are required to reduce non-adherence, improve patient outcomes and limit the risk of selecting drug-resistant strains. METHODS: We performed a retrospective cohort study in sputum smear-positive patients treated with community-based DOT (home-based DOT or 'lunch' DOT, whereby DOT is provided with a free daily meal once sputum smear conversion has been documented), and conventional clinic-based DOT in Ulaanbaatar, the capital of Mongolia, in 2010-2011. We compared treatment success using community-based home DOT vs. conventional clinic DOT and describe treatment completion rates using lunch DOT. RESULTS: The overall treatment success among new sputum smear-positive TB patients was 85.1% (1505/1768). Patients receiving community DOT had higher cure rates (294/327, 89.9% vs. 1112/1441, 77.2%; aOR 2.66, 95%CI 1.81-3.90) and higher treatment success (306/327, 93.6% vs. 1199/1441, 83.2%; aOR 2.95, 95%CI 1.85-4.71, P < 0.001) than those treated with clinic DOT. Apart from one death, treatment completion was 100% among patients who received lunch DOT after sputum smear conversion. CONCLUSIONS: Community DOT improved treatment success in Ulaanbaatar, Mongolia. It should now be scaled up to be made available for more patients and in all regions of the country.

Associations between milk protein polymorphisms and milk production traits.

Associations between milk protein genotypes and milk production traits were estimated from 6803 first lactation records. Exact tests of associated hypotheses and unbiased estimates of genotype effects were from an animal model. Milk protein genotype effects were estimated using a model in which each milk protein gene was analyzed separately (single-gene analysis) and a model in which all milk protein genes were analyzed simultaneously (multigene analysis). The results of the two models indicate that some effects ascribed to certain milk protein genes in the single-gene analysis are not effects of the milk protein gene itself but of linked genes. Results from this study and from literature indicate that the kappa-casein gene or a very closely linked gene affects protein percentage, and the beta-lactoglobulin gene or a very closely linked gene affects fat percentage. Furthermore, effects of beta-casein genotypes on milk production, fat percentage, and protein yield were significant, and beta-lactoglobulin genotypes had significant effects on milk production and protein yield. It is less clear whether those effects are due to effects of milk protein genes themselves or to effects of linked genes.