A Cost Utility Analysis of Minimally Invasive Surgery with Thrombolysis Compared to Standard Medical Treatment in Spontaneous Intracerebral Haemorrhagic Stroke.

OBJECTIVES: Standard medical management of spontaneous intracerebral haemorrhage (ICH) and surgical hematoma evacuation starkly differ, and whilst landmark randomised control trials report no clinical benefit of early surgical evacuation compared with medical treatment in supratentorial ICH, minimally invasive surgery (MIS) with thrombolysis has been neglected within these studies. However, recent technological advancements in MIS have renewed interest in the surgical treatment of ICH. Several economic evaluations have focused on the benefits of MIS in ischaemic stroke management, but no economic evaluations have yet been performed comparing MIS to standard medical treatment for ICH. MATERIALS AND METHOD: All costs were sourced from the UK in GBP. Where possible, the 2019/2020 NHS reference costs were used. The MISTIE III study was used to analyse the outcomes of patients undergoing either MIS or standard medical treatment in this economic evaluation. RESULTS: The incremental cost-effectiveness ratio (ICER) for MIS was £485,240.26 for every quality-adjusted life year (QALY) gained. Although MIS resulted in a higher QALY compared to medical treatment, the gain was insignificant at 0.011 QALY. Four sensitivity analyses based on combinations of alternative EQ-5D values and categorisation of MIS outcomes, alongside alterations to the cost of significant adverse events, were performed to check the robustness of the ICER calculation. The most realistic sensitivity analysis showed a potential increase in cost effectiveness when clot size is reduced to <15ml, with the ICER falling to £74,335.57. DISCUSSION: From the perspective of the NHS, MIS with thrombolysis is not cost-effective compared to optimal medical treatment. ICER shows that intention-to-treat MIS would require a cost of £485,240.26 to gain one extra QALY, which is significantly above the NHS threshold of £30,000. Further UK studies with ICH survivor utilities, more replicable surgical technique, and the reporting of clot size reduction are indicated as the present sensitivity analysis suggests that MIS is promising. Greater detail about outcomes and complications would ensure improved cost-benefit analyses and support valid and efficient allocation of resources by the NHS.

Effects of Antipsychotic Drugs: Cross Talk Between the Nervous and Innate Immune System.

Converging lines of evidence suggest that activation of microglia (innate immune cells in the central nervous system [CNS]) is present in a subset of patients with schizophrenia. The extent to which antipsychotic drug treatment contributes to or combats this effect remains unclear. To address this question, we reviewed the literature for evidence that antipsychotic exposure influences brain microglia as indexed by in vivo neuroimaging and post-mortem studies in patients with schizophrenia and experimental animal models. We found no clear evidence from clinical studies for an effect of antipsychotics on either translocator protein (TSPO) radioligand binding (an in vivo neuroimaging measure of putative gliosis) or markers of brain microglia in post-mortem studies. In experimental animals, where drug and illness effects may be differentiated, we also found no clear evidence for consistent effects of antipsychotic drugs on TSPO radioligand binding. By contrast, we found evidence that chronic antipsychotic exposure may influence central microglia density and morphology. However, these effects were dependent on the dose and duration of drug exposure and whether an immune stimulus was present or not. In the latter case, antipsychotics were generally reported to suppress expression of inflammatory cytokines and inducible inflammatory enzymes such as cyclooxygenase and microglia activation. No clear conclusions could be drawn with regard to any effect of antipsychotics on brain microglia from current clinical data. There is evidence to suggest that antipsychotic drugs influence brain microglia in experimental animals, including possible anti-inflammatory actions. However, we lack detailed information on how these drugs influence brain microglia function at the molecular level. The clinical relevance of the animal data with regard to beneficial treatment effects and detrimental side effects of antipsychotic drugs also remains unknown, and further studies are warranted.