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Background and purpose: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti‐inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti‐inflammatory disease‐modifying treatment on disability outcomes in PPMS. Methods: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease‐modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention‐to‐treat and an as‐treated approach in paired, pairwise‐censored analyses. Results: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on‐study pairwise‐censored follow‐up was 3.4 years (quartiles 1.2–5.5). No difference in the hazard of experiencing 3‐month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6–1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6–1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7–1.6, P = 0.69). Conclusion: Our pooled analysis of disease‐modifying agents suggests that these therapies have no substantial effect on short‐ to medium‐term disability outcomes in PPMS. [ABSTRACT FROM AUTHOR]

Abstract: We report a previously undescribed 7676 base pair mitochondrial (mt)DNA deletion involving genes of complex I, complex IV subunits 2 and 3 (cytochrome oxidase [Cox] II, III), adenosine triphosphatase 8 and 6, cytochrome b and 8 transfer (t)RNA genes producing myopathy and progressive external ophthalmoplegia (PEO) in a 44-year-old right-handed Caucasian man with features of multiple sclerosis (MS). We performed complete mtDNA sequencing and deletion analysis, spectrophotometric analysis of muscle and platelet respiratory chain activity, measurement of platelet mitochondrial membrane potential with the potentiometric dye JC-1 and magnetic resonance spectroscopy (MRS) and MRI studies of normal-appearing and lesional cerebral tissue. The deletion resulted in significant respiratory chain deficiency in muscle and blood and abnormalities of the platelet mitochondrial membrane potential. However, cerebrospinal fluid analysis, magnetic resonance spectroscopy and MRI features suggested inflammatory central nervous system demyelination rather than a primary respiratory chain disorder. We conclude that this novel mtDNA deletion causing myopathy and PEO is associated with severe muscle and platelet cellular energetic abnormalities. Furthermore, clinical and paraclinical features of multiple sclerosis were found. The potential pathomechanistic interaction between mtDNA variation and multiple sclerosis is reviewed. [Copyright &y& Elsevier]

• Utilisation studies inform safe and effective medicines use. • The Australian market was responsive to 13 new medicines over 14 years. • Incidence and prevalence use increased by 20% and 88%, respectively. • Diverse treatment pathways were found with exposure to multiple medicines over time. • Findings can contribute to developing post market surveillance studies. There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). A representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006–2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006–2013 and 2014–2019). There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006–2013 and 28.5% of initiators in 2014–2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006–2013 and 2014–2019, respectively. The availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems. [ABSTRACT FROM AUTHOR]

AbstractThe floral visitors of silky oak, Grevillea robusta A. Cunn. ex R.Br., their foraging behaviour and their effects on fruit-set were studied at Malava, western Kenya. Grevillea robusta is a popular tree for farm plantings in the eastern and central African highlands. Yield of seed has been disappointingly low in some areas and a lack of appropriate pollinators has been suggested as a possible cause. Investigations involved the monitoring of visitors on active inflorescences, assessment of the rewards available to potential pollinators, and exclusion experiments to establish the effects of various visitors on fruit-set. The flowers are visited mainly by birds and insects. The likely pollinators of G. robusta are sunbirds (Nectarinia amethystina, N. cyanolaema, N. olivacea, N. superba and N. venusta) and white-eyes (Zosterops kikuyuensis and Z. senegalensis). Very little aggressive behaviour between birds was recorded. No nocturnal pollinators were observed. Nectar was the major floral reward for pollinators, but is likely depleted by ants and honey bees, the foraging behaviour of which confirmed them to be nectar-robbers. These insects hardly ever touched stigmas during their visits. Eighty-nine per cent of bird visits were in the morning (07.00–10.00 hours) when nectar volume was highest. Inflorescences bagged to exclude birds set no fruits, and unmanipulated flowers and flowers bagged with self-pollen set no fruits, indicating a self-incompatibility mechanism. Control cross-pollinated flowers displayed greatly increased fruit-set (25.1%) compared with natural open-pollination (0.9%). All these findings confirm the importance of cross-pollen transfer to flowers and the necessity of pollinators for fruit-set. Effective seed production requires activity of pollinators for self-pollen removal and cross-pollen deposition. Seed production stands for G. robusta should be established where flowering is prolific and bird pollinators are abundant. [ABSTRACT FROM AUTHOR]