Prevalence and Impact of Diabetes Mellitus on the Frozen Shoulder.

OBJECTIVES: The objective of this study was to estimate the prevalence of undiagnosed diabetes mellitus in patients with newly diagnosed frozen shoulder (FS) and study whether diabetes mellitus increases the severity of FS disease. METHODS: Patients with newly diagnosed FS were consecutively included in this case-control study. Patients who were not already diagnosed as having diabetes mellitus were invited to be tested with the hemoglobin A1c blood sample test. The study population was compared with a control group, consisting of five individuals from the general population matched on age and sex. The passive range of motion, Oxford Shoulder Score, and visual analog scale (VAS) for average and maximum daily pain was recorded for all of the patients in the study group. RESULTS: A total of 235 patients were included, 34 (14%) of whom were diagnosed as having diabetes mellitus before the examination. Of the remaining 201 patients, 122 (61%) agreed to be tested for diabetes mellitus. None of the tested patients had undiagnosed diabetes mellitus. This was not significantly different from the prevalence in the matched control population (P = 0.09). There was no difference between patients with and without diabetes mellitus in average daily VAS (P = 0.46) nor maximum daily VAS (P = 0.44). The Oxford Shoulder Score was similar in the two groups (P = 0.23) as was the range of motion. CONCLUSIONS: The prevalence of undiagnosed diabetes mellitus is low in patients with FS and does not differ from the general population. Diabetes mellitus does not seem to affect patients' perceived severity of an FS.

A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models.

Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII-polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10 to 80 kDa) selectively to a unique O-linked glycan in the FVIII B-domain. Binding to von Willebrand factor (VWF) was maintained for all conjugates. Upon cleavage by thrombin, the B-domain and the associated PEG were released, generating activated FVIII (FVIIIa) with the same primary structure and specific activity as native FVIIIa. In both FVIII- and VWF-deficient mice, the half-life was found to increase with the size of PEG. In vivo potency and efficacy of FVIII conjugated with a 40-kDa PEG (N8-GP) and unmodified FVIII were not different. N8-GP had a longer duration of effect in FVIII-deficient mouse models, approximately a twofold prolonged half-life in mice, rabbits, and cynomolgus monkeys; however, the prolongation was less pronounced in rats. Binding capacity of N8-GP on human monocyte-derived dendritic cells was reduced compared with unmodified FVIII, resulting in several-fold reduced cellular uptake. In conclusion, N8-GP has the potential to offer efficacious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency.