Costs,effects and cost‐effectiveness of breast cancer control in Ghana

Objective Breast cancer control in Ghana is characterised by low awareness, late‐stage treatment and poor survival. In settings with severely constrained health resources, there is a need to spend money wisely. To achieve this and to guide policy makers in their selection of interventions, this study systematically compares costs and effects of breast cancer control interventions in Ghana. Methods We used a mathematical model to estimate costs and health effects of breast cancer interventions in Ghana from the healthcare perspective. Analyses were based on the WHO‐CHOICE method, with health effects expressed in disability‐adjusted life years (DALYs), costs in 2009 US dollars (US$) and cost‐effectiveness ratios (CERs) in US$ per DALY averted. Analyses were based on local demographic, epidemiological and economic data, to the extent these data were available. Results Biennial screening by clinical breast examination (CBE) of women aged 40–69 years, in combination with treatment of all stages, seems the most cost‐effective intervention (costing $1299 per DALY averted). The intervention is also economically attractive according to international standards on cost‐effectiveness. Mass media awareness raising (MAR) is the second best option (costing $1364 per DALY averted). Mammography screening of women of aged 40–69 years (costing $12 908 per DALY averted) cannot be considered cost‐effective. Conclusions Both CBE screening and MAR seem economically attractive interventions. Given the uncertainty about the effectiveness of these interventions, only their phased introduction, carefully monitored and evaluated, is warranted. Moreover, their implementation is only meaningful if the capacity of basic cancer diagnostic, referral and treatment and possibly palliative services is simultaneously improved.     

Experimental parameter estimation of a visuo-vestibular interaction model in humans

Visuo-vestibular interactions in monkeys can be accurately modelled using the classical Raphan and Cohen's model. This model is composed of direct vestibular and visual contributions to the vestibulo-ocular reflex (VOR) and of a velocity storage. We applied this model to humans and estimated its parameters in a series of experiments: yaw rotations at moderate (60°/s) and high velocities (240°/s), suppression of the VOR by a head-fixed wide-field visual stimulus, and optokinetic stimulation with measurements of optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN). We found the velocity storage time constant to be 13 s, which decreased to 8 s during visual suppression. OKAN initial velocity was 12% of the OKN stimulus velocity. The gain of the direct visual pathway was 0.75 during both visual suppression and OKN; however, the visual input to the velocity storage was higher during visual suppression than during OKN. We could not estimate the time constant of the semicircular canals accurately. Finally, we inferred from high-velocity rotations that the velocity storage saturates around 20-30°/s. Our results indicate that the dynamics of visuo-vestibular interactions in humans is similar as in monkeys. The central integration of visual cues, however, is weaker in humans.     

Purkinje Cell Input to Cerebellar Nuclei in Tottering: Ultrastructure and Physiology

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei. Freek E. Hoebeek and Sara Khosrovani contributed equally.     

Optical coherence tomography-derived predictors of stent expansion in calcified lesions

Background

Severe coronary artery calcification is associated with stent underexpansion and subsequent stent failure.

Aims

We aimed to identify optical coherence tomography (OCT)-derived predictors of absolute (minimal stent area [MSA]) and relative stent expansion in calcified lesions.

Methods

This retrospective cohort study included patients who underwent percutaneous coronary intervention (PCI) with OCT assessment before and after stent implantation between May 2008 and April 2022. Pre-PCI OCT was used to assess calcium burden and post-PCI OCT was used to assess absolute and relative stent expansion.

Results

A total of 361 lesions in 336 patients were analyzed. Target lesion calcification (defined as OCT-detected maximum calcium angle ≥ 30°) was present in 242 (67.0%) lesions. Following PCI, median MSA was 5.37 mm² in calcified lesions and 6.24 mm² in noncalcified lesions (p < 0.001). Median stent expansion was 78% in calcified lesions and 83% in noncalcified lesions (p = 0.325). In the subset of calcified lesions, average stent diameter, preprocedural minimal lumen area, and total calcium length were independent predictors of MSA in multivariable analysis (mean difference 2.69 mm²/mm², 0.52 mm²/mm, and −0.28 mm²/5 mm, respectively, all p < 0.001). Total stent length was the only independent predictor of relative stent expansion (mean difference −0.465% per mm, p < 0.001). Calcium angle, thickness, and the presence of nodular calcification were not significantly associated with MSA or stent expansion in multivariable analyses.

Conclusion

Calcium length appeared to be the most important OCT-derived predictor of MSA, whereas stent expansion was mainly determined by total stent length.