Determinants of patient and surgeon perspectives on maximum acceptable waiting times for hip and knee arthroplasty

OBJECTIVES: Lengthy waiting times for hip and knee arthroplasty have raised concerns about equitable and timely access to care. The Western Canada Waiting List project has developed priority criteria scores linked to maximum acceptable waiting times (MAWT) for different levels of priority. Our study purpose was to assess the determinants of patient- and surgeon-rated MAWT, and to test whether the anticipated waiting time has an independent influence after adjusting for age, sex and patient urgency. A second aim was to compare MAWT, waiting time and anticipated waiting time for different levels of urgency assessed using the priority criteria score. METHODS: Orthopaedic surgeons assessed 233 consecutive patients waiting for arthroplasty in terms of their urgency (assessed using the priority criteria score and a visual analogue scale), MAWT and anticipated waiting time. Patient data included urgency (assessed by a visual analogue scale), MAWT and the Western Ontario McMaster Osteoarthritis index. We used hierarchical linear regression to test the models. RESULTS: After adjusting for age and sex, urgency (assessed by priority criteria score and visual analogue scale) and anticipated waiting time accounted for 40% of the variance in surgeon MAWT. The patient model accounted for 30% of the variance in patient MAWT. Older patients preferred signficantly shorter MAWTs (P <0.05). Anticipated waiting time added significantly to both the surgeon and patient MAWT models (R(2) change 0.11 and 0.07, respectively). Actual waiting time was weakly correlated with urgency assessed using the priority criteria score (r = -0.25, P <0.0001). CONCLUSIONS: Patients' and surgeons' views are critical to a fair process of establishing MAWT for elective procedures. Anticipated waiting time may influence the perspectives on MAWT and must be considered in their interpretation.     

Internalization of gonadotropin-releasing hormone receptors (GnRHRs): does arrestin binding to the C-terminal tail target GnRHRs for dynamin-dependent internalization?

Activation of seven-transmembrane receptors is typically followed by desensitization and arrestin-dependent internalization via vesicles that are pinched off by a dynamin collar. Arrestins also scaffold Src, which mediates dynamin-dependent internalization of beta2-adrenergic receptors. Type I mammalian gonadotropin-releasing hormone receptors (GnRHRs) do not rapidly desensitize or internalize (characteristics attributed to their unique lack of C-terminal tails) whereas non-mammalian GnRHRs (that have C-terminal tails) are rapidly internalized and desensitized. Moreover, internalization of Xenopus (X) GnRHRs is dynamin-dependent whereas that of human (h) GnRHRs is not, raising the possibility that binding of arrestin to the C-terminal tails of GnRHRs targets them to the dynamin-dependent internalization pathway. To test this we have compared wild-type GnRHRs with chimeric receptors (XGnRHR C-terminal tail added to the hGnRHR alone (h.XtGnRHR) or with exchange of the third intracellular loops (h.Xl.XtGnRHR)). We show that adding the XGnRHR C-terminal tail facilitates arrestin- and dynamin-dependent internalization as well as arrestin/green fluorescent protein translocation, but Src (or mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) inhibition does not slow internalization, and h.XtGnRHR internalization is slower than that of the hGnRHR. Moreover, arrestin expression increased XGnRHR internalization even when dynamin was inhibited and h.Xl.XtGnRHR underwent rapid arrestin-dependent internalization without signaling to G(q/11). Thus, although the C-terminal tail can direct GnRHRs for arrestin- and dynamin-dependent internalization, this effect is not dependent on Src activation and arrestin can also facilitate dynamin-independent internalization.