Lessons learnt from syphilis-infected blood donors: a timely reminder of missed opportunities.

OBJECTIVE: Due to the increased number of syphilis infections diagnosed in the UK and beyond, we reviewed our data on blood donors infected with syphilis in the UK and Ireland between 2016 and 2019. METHODS: Data were extracted from the surveillance database for all blood donors confirmed positive for syphilis in the UK and Ireland between 2016 and 2019, together with the total number of donations tested during that period. Data on positive cases included gender, age group, reported treatment, symptoms and confirmatory results. All cases were divided into recently acquired within 24 months and past syphilis infection. We also reviewed the information on symptoms characteristic of syphilis reported by blood donors with an untreated syphilis infection during the postdonation discussions. RESULTS: Screening of 8 246 600 blood donations for treponemal antibodies identified 316 blood donors with confirmed syphilis infection in the UK and Ireland between 2016 and 2019 (1.6 per 100 000 donations). 42% of them (133 of 316) were classed as a recent infection based on their donation testing results, previous donation date and clinical history provided, and they were hence considered potentially infectious. Most of these blood donors (202 of 316, 64%) had not been previously diagnosed or treated for syphilis, although 50 of them reported symptoms consistent with syphilis infection and 19 had been misdiagnosed despite seeking medical help. CONCLUSIONS: This observational study shows that syphilis infection remains undiagnosed, especially among heterosexual men, and that infectious syphilis is often missed as a differential diagnosis even when donors have presented with genital or oral ulceration, rashes in the genital area and lymphadenopathy. Considering the recent resurgence of syphilis infections in the UK and beyond and our generally expanding sexual networks, it is important to consider syphilis in differential diagnosis even if specific risk factors have not been identified.

In vitro fertilisation with recombinant follicle stimulating hormone requires less IU usage compared with highly purified human menopausal gonadotrophin: results from a European retrospective observational chart review.

BACKGROUND: Previous studies have reported conflicting results for the comparative doses of recombinant follicle stimulating hormone (rFSH) and highly purified human menopausal gonadotrophin (hMG-HP) required per cycle of in vitro fertilisation (IVF); the aim of this study was to determine the average total usage of rFSH versus hMG-HP in a 'real-world' setting using routine clinical practice. METHODS: This retrospective chart review of databases from four European countries investigated gonadotrophin usage, oocyte and embryo yield, and pregnancy outcomes in IVF cycles (± intra-cytoplasmic sperm injection) using rFSH or hMG-HP alone. Included patients met the National Institute for Health and Clinical Excellence (NICE) guideline criteria for IVF and received either rFSH or hMG-HP. Statistical tests were conducted at 5% significance using Chi-square or t-tests. RESULTS: Of 30,630 IVF cycles included in this review, 74% used rFSH and 26% used hMG-HP. A significantly lower drug usage per cycle for rFSH than hMG-HP (2072.53 +/- 76.73 IU vs. 2540.14 +/- 883.08 IU, 22.6% higher for hMG-HP; p < 0.01) was demonstrated. The median starting dose was also significantly lower for rFSH than for hMG-HP (150 IU vs. 225 IU, 50% higher for hMG-HP, p < 0.01). The average oocyte yield per IVF cycle in patients treated with rFSH was significantly greater than with hMG-HP (10.80 +/- 6.02 vs. 9.77 +/- 5.53; p < 0.01), as was the average mature oocyte yield (8.58 +/- 5.27 vs. 7.72 +/- 4.59; p < 0.01). No significant differences were observed in pregnancy outcomes including spontaneous abortion between the two treatments. There was a significantly higher rate of OHSS (all grades) with rFSH (18.92% vs. 14.09%; p < 0.0001). The hospitalisation rate due to OHSS was low but significantly higher in the rFSH group (1.07% of cycles started vs. 0.67% of cycles started with rFSH and hMG-HP, respectively; p = 0.002). CONCLUSIONS: Based on these results, IVF treatment cycles with rFSH yield statistically more oocytes (and more mature oocytes), using significantly less IU per cycle, versus hMG-HP. The incidence of all OHSS and hospitalisations due to OHSS was significantly higher in the rFSH cycles compared to the hMG-HP cycles. However, the absolute incidence of hospitalisations due to OHSS was similar to that reported previously. These results suggest that the perceived required dosage with rFSH is currently over-estimated, and the higher unit cost of rFSH may be offset by a lower required dosage compared with hMG-HP.

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial.

BACKGROUND: We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis (MS). The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants. The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS. Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS, including mechanisms underlying repair. METHODS/DESIGN: A prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n = 20) will have primary progressive disease (PPMS). Participants will be randomised to either early or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analysed on an intention-to-treat basis. DISCUSSION: Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS) is the first randomised, placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS. It will determine whether bone marrow cell therapy can, as was suggested by the phase I safety study, improve conduction in multiple central nervous system pathways affected in progressive MS. Furthermore, laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy. TRIAL REGISTRATION: ISRCTN27232902 Registration date 11/09/2012. NCT01815632 Registration date 19/03/2013.