Reply to the letter by Prof. Rothschild. DOI: 10.1007/s10067-019-04560-y
Dear Editor in Chief, We would like to thank Professor Rothschild for his interest in our article and the opportunity to respond to his letter, where he describes Btwo fundamental methodologic flaws^ with regard to our GLUTEAL study, evaluating the role for glucocorticoid injections in the greater trochanteric pain syndrome (GTPS) [1]. His first point relates to betamethasone being water soluble. As described in our publication, the glucocorticoid preparation utilized was Diprophos®, which consists of a mixture of betamethasone disodium phosphate and betamethasone dipropionate. The betamethasone disodium phosphate is indeed water soluble, whereas the betamethasone dipropionate has poor water solubility as it forms local crystal deposits, which explains the prolonged clinical effect of this substance. The second point addresses the number of bursa in the region of the greater trochanter, and Professor Rothschild suggests that there are a total of four. Indeed, we could have been more specific, but generally when one describes the grater trochanteric bursa, it implies the deep subgluteus maximus bursa, which lies beneath the gluteus maximus muscle and iliotibial band, and superficial to the gluteus medius tendon. In the paper by Williams et al. cited in his letter, the authors in fact describe nine different bursae in the region of the greater trochanter that have been potentially implicated in the GTPS, although in most cases either the deep subgluteus maximus bursa or the subgluteus medius bursa is involved [2]. In our experience, the identification of the majority of these bursae with ultrasound is extremely difficult, unless there is a pathological collection of fluid within them. We are not aware of any publication suggesting that the injection of multiple bursae around the greater trochanter has a greater clinical efficacy compared with the injection of a single bursa. In a retrospective review including 65 ultrasound-guided glucocorticoid injections for the GTPS, there was a significantly greater efficacy of injections into the greater trochanteric (deep subgluteus maximus) bursa compared with the subgluteus medius bursa, and that injections into the subgluteus medius bursa were of no clinical benefit [3]. It should be highlighted that imaging evidence of a bursitis is only found in a minority of cases of the GTPS. For example, in the seminal paper by Bird et al., only 8% patients with GTPS demonstrated MRI evidence of bursitis [4]. Other publications have found imaging evidence of bursitis in 15 to 40% of cases of GTPS. Finally, Professor Rothschild states that Ball four bursae are inflamed, or at least sources of clinical symptoms, in almost all individuals^ with GTPS and in the World Journal of Orthopedics, he describes the immediate elimination of pain in 49/50 individuals from his own practice with trochanteric pain in whom four bursae were injected with triamcinolone, with pain relief persisting for greater than 6 months in 47 individuals [5]. It would indeed be very interesting to test this hypothesis in a randomized controlled trial. See related article, https://doi.org/10.1007/s10067-019-04560-y.
Trochanteric area pain, the result of a quartet of bursal inflammation.
Bursitis is quite responsive to therapeutic intervention, once the afflicted area is accurately identified. This is especially notable for some hip complaints. Patients' use of the term "hip" can relate to anything from the low back to groin to lateral thigh pain. Trochanteric area surface localization of "hip" pain may afford an opportunity for immediate cure. Effectiveness of therapeutic intervention is predicated upon injection of not one or two, but all four peri-trochanteric bursa with a depot (minimally water-soluble) corticosteroid. The term trochanteric bursitis suggests that the inflammation is more focal than what is clinically observed. While easier to express, perhaps it is time to refer to inflammation in this area, naming all four affected bursae.
Second-Generation Process Research Towards Eletriptan: A Fischer Indole Approach
The development of a second-generation process for the synthesis of eletriptan via a Fischer indole cyclisation is described. The finalised process offers several potential advantages over the current route of manufacture including cost, throughput, and safety.