ABSTRACT
PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.
Subject(s)
Cystic Fibrosis , Diabetes Mellitus , Biomarkers , Canada , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Diabetes Mellitus/epidemiology , Diabetes Mellitus/genetics , Genome-Wide Association Study , Humans , Infant, NewbornABSTRACT
The objective of this case report was to review acquired canine urethral incontinence in a case of a 2-year-old beagle that presented for inappropriate urination. Commercially available medications, as well as compounded medical therapeutic options, were reviewed. Diagnostic results revealed cystitis, which responded to the prescribed antibiotics. The incontinence issue remained. Compounded diethylstilbestrol was prescribed and dispensed to achieve successful clinical results. The role of the compounding pharmacist was vital to achieve appropriate dosing of a drug no longer commercially available.
Subject(s)
Dog Diseases/drug therapy , Urinary Incontinence/veterinary , Animals , Diethylstilbestrol/therapeutic use , Dog Diseases/diagnosis , Dogs , Estriol/therapeutic use , Female , Phenylpropanolamine/therapeutic use , Urinary Incontinence/diagnosis , Urinary Incontinence/drug therapyABSTRACT
PURPOSE: Total and partial urogenital mobilization procedures are the most common contemporary vaginoplasty surgeries for patients with congenital adrenal hyperplasia, urogenital sinus and cloacal anomalies. There is controversy regarding the urinary continence outcomes of these procedures. We reviewed the urinary continence outcomes of children who underwent total or partial urogenital mobilization at our institution and reviewed the literature to determine the continence rates of these procedures. MATERIALS AND METHODS: We retrospectively reviewed 25 patients who underwent total or partial urogenital mobilization with a focus on postoperative continence status. Continence was defined as parental report of full toilet training with no accidents during the day and rare accidents (fewer than 2 per month) at night after age 3 years. RESULTS: A total of 14 congenital adrenal hyperplasia, 5 urogenital sinus and 6 cloacal anomaly cases were managed by total (18) or partial (7) urogenital mobilization procedures with a mean followup of 4.41 years (range 0.21 to 12.1). In our cohort 21 of 22 patients (95.5%) were continent by age 3 years and there were no urinary complications. A total of 111 patients were identified in the literature with congenital adrenal hyperplasia or urogenital sinus, with 107 in 7 studies being continent (96.4%) by age 3 to 4 years. In 4 studies 32 patients were identified with cloacal anomalies who underwent total or partial urogenital mobilization, of whom 28 (87.5%) were continent by age 3 to 4 years. CONCLUSIONS: There was no significant difference between total and partial urogenital mobilization procedures regarding postoperative urinary continence in our cohort and the literature. The urinary continence rate was 96% in the congenital adrenal hyperplasia/urogenital sinus group and 89.5% in the cloacal group.
