Perioperative shared decision making - How do we train clinicians?

Objective: Decision making about high-risk surgery can be complex, particularly when outcomes may be uncertain. Clinicians have a legal and ethical responsibility to support decision making which fits with patients' values and preferences. In the UK, preoperative assessment and optimisation is led by Anaesthetists in clinic several weeks prior to planned surgery. Training in supporting shared decision making (SDM) has been identified as an area of need among UK anaesthetists with leadership roles in perioperative care. Methods: We describe adaptation of a generic SDM workshop to perioperative care, in particular to decisions on high-risk surgery, and its delivery to UK healthcare professionals over a two-year period. Feedback from workshops were thematically analysed. We explored further improvements to the workshop and ideas for development and dissemination. Results: The workshops were well received, with high satisfaction for techniques used, including video demonstrations, role-play and discussions. Thematic analysis identified a desire for multidisciplinary training and training in using patient aids. Conclusion: Qualitative findings suggest workshops were considered useful with perceived improvement in SDM awareness, skills and reflective practice. Innovation: This pilot introduces a new modality of training in the perioperative setting providing physicians, particularly Anaesthetists, with previously unavailable training needed to facilitate complex discussions.

High diagnostic rate of trio exome sequencing in consanguineous families with neurogenetic diseases.

Consanguineous marriages have a prevalence rate of 24% in Turkey. These carry an increased risk of autosomal recessive genetic conditions, leading to severe disability or premature death, with a significant health and economic burden. A definitive molecular diagnosis could not be achieved in these children previously, as infrastructures and access to sophisticated diagnostic options were limited. We studied the cause of neurogenetic disease in 246 children from 190 consanguineous families recruited in three Turkish hospitals between 2016 and 2020. All patients underwent deep phenotyping and trio whole exome sequencing, and data were integrated in advanced international bioinformatics platforms. We detected causative variants in 119 known disease genes in 72% of families. Due to overlapping phenotypes 52% of the confirmed genetic diagnoses would have been missed on targeted diagnostic gene panels. Likely pathogenic variants in 27 novel genes in 14% of the families increased the diagnostic yield to 86%. Eighty-two per cent of causative variants (141/172) were homozygous, 11 of which were detected in genes previously only associated with autosomal dominant inheritance. Eight families carried two pathogenic variants in different disease genes. De novo (9.3%), X-linked recessive (5.2%) and compound heterozygous (3.5%) variants were less frequent compared to non-consanguineous populations. This cohort provided a unique opportunity to better understand the genetic characteristics of neurogenetic diseases in a consanguineous population. Contrary to what may be expected, causative variants were often not on the longest run of homozygosity and the diagnostic yield was lower in families with the highest degree of consanguinity, due to the high number of homozygous variants in these patients. Pathway analysis highlighted that protein synthesis/degradation defects and metabolic diseases are the most common pathways underlying paediatric neurogenetic disease. In our cohort 164 families (86%) received a diagnosis, enabling prevention of transmission and targeted treatments in 24 patients (10%). We generated an important body of genomic data with lasting impacts on the health and wellbeing of consanguineous families and economic benefit for the healthcare system in Turkey and elsewhere. We demonstrate that an untargeted next generation sequencing approach is far superior to a more targeted gene panel approach, and can be performed without specialized bioinformatics knowledge by clinicians using established pipelines in populations with high rates of consanguinity.

Concentration and sources of fine particulate associated polycyclic aromatic hydrocarbons at two locations in the western coast of India.

PM2.5 particulate matter (PM) and their associated polycyclic aromatic hydrocarbons (PAHs) were studied at Urban and Sub-urban sites in the western coast of India. The concentration of PM2.5 ranged from 66.29 µg m-3 to 182.15 µg m-3, being the highest at Sub-urban site than the urban site. There were total six carcinogenic PAHs found to be dominated in particulate samples at these locations. The general trends observed for individual carcinogenic PAHs concentration at urban location was, benzo(a)pyrene (BaP)

Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior.

Major depressive disorder (MDD) is one of the most common and debilitating neuropsychiatric illnesses. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of MDD. The complement system represents one of the major effector mechanisms of the innate immune system, and plays a critical role in inflammation. However, the role of complement components in MDD is not well understood. Here, we found significant increase in component 3 (C3) expression in the prefrontal cortex (PFC) of depressed suicide subjects. We tested the role of altered C3 expression in mouse model of depression and found that increased C3 expression in PFC as a result of chronic stress causes depressive-like behavior. Conversely, mice lacking C3 were resilient to stress-induced depressive-like behavior. Moreover, selective overexpression of C3 in PFC was sufficient to cause depressive-like behavior in mice. We found that C3a (activated product of C3) receptor, C3aR+ monocytes were infiltrated into PFC following chronic stress. However, C3aR knockout mice displayed significantly reduced monocyte recruitment into PFC and reduced levels of the proinflammatory cytokine IL-1ß in PFC after chronic stress. In addition, C3aR knockout mice did not exhibit chronic stress-induced behavior despair. Similarly, chronic stress-induced increases in C3aR+ monocytes and IL-1ß in PFC, and depressive-like behavior were attenuated by myeloid cell depletion. These postmortem and preclinical studies identify C3aR signaling as a key factor in MDD pathophysiology.