Background The number of patients living with co-existing diseases is growing. This study aimed to assess the extent of multimorbidity, medication use, and drug- and gene-based interactions in patients following a non-ST elevation acute coronary syndrome (NSTE-ACS). Methods In 1456 patients discharged from hospital for a NSTE-ACS, comorbidities and multimorbidity (≥ 2 chronic conditions) were assessed. Of these, 698 had complete drug use recorded at discharge, and 652 (the ‘interaction’ cohort) had drug use and actionable genotypes available for CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, SLCO1B1, TPMT, UGT1A1, and VKORC1. The following drug interactions were investigated: pharmacokinetic drug-drug (DDIs) involving CYPs (CYPs above, plus CYP1A2, CYP2C8, CYP3A4), SLCO1B1, and P-glycoprotein; drug-gene (DGIs); drug-drug-gene (DDGIs); and drug-gene-gene (DGGIs). Interactions predicted to be ‘substantial’ were defined as follows: DDIs due to strong inhibitors/inducers, DGIs due to variant homozygous/compound heterozygous genotypes, and DDGIs/DGGIs where the constituent DDI/DGI(s) both influenced the victim drug in the same direction. Results In the whole cohort, 727 (49.9%) patients had multimorbidity. Non-linear relationships between age and increasing comorbidities and decreasing coronary intervention were observed. There were 98.1% and 39.8% patients on ≥ 5 and ≥ 10 drugs, respectively (from n = 698); women received more non-cardiovascular drugs than men (median (IQR) 3 (1–5) vs 2 (1–4), p = 0.014). Overall, 98.7% patients had at least one actionable genotype. Within the interaction cohort, 882 interactions were identified in 503 patients (77.1%), of which 346 in 252 patients (38.7%) were substantial: 59.2%, 11.6%, 26.3%, and 2.9% substantial interactions were DDIs, DGIs, DDGIs, and DGGIs, respectively. CYP2C19 (49.5% of all interactions) and SLCO1B1 (18.4%) were involved in the largest number of interactions. Multimorbidity (p = 0.019) and number of drugs (p = 9.8 × 10−10) were both associated with patients having ≥ 1 substantial interaction. Multimorbidity (HR 1.76, 95% CI 1.10–2.82, p = 0.019), number of drugs (HR 1.10, 95% CI 1.04–1.16, p = 1.2 × 10−3), and age (HR 1.05, 95% CI 1.03–1.07, p = 8.9 × 10−7), but not drug interactions, were associated with increased subsequent major adverse cardiovascular events. Conclusions Multimorbidity, polypharmacy, and drug interactions are common after a NSTE-ACS. Replication of results is required; however, the high prevalence of DDGIs suggests integrating co-medications with genetic data will improve medicines optimisation.

Importance: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population.Objective: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years.Evidence Review: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS.Findings: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, −0.35 [95% confidence interval, −0.68 to −0.03; P = 0.0351]; AS: standardized mean difference, −0.74 [95% CI, −1.37 to −0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression.Conclusions and Relevance: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

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Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.

The somatosensory system is multidimensional and processes important information for survival, including the experience of pain. The brainstem and spinal cord serve pivotal roles in both transmitting and modulating pain signals from the periphery; although, they are studied less frequently with neuroimaging when compared to the brain. In addition, imaging studies of pain often lack a sensory control condition, failing to differentiate the neural processes associated with pain versus innocuous sensations. The purpose of this study was to investigate neural connectivity between key regions involved in descending modulation of pain in response to a hot, noxious stimulus as compared to a warm, innocuous stimulus. This was achieved with functional magnetic resonance imaging (fMRI) of the brainstem and spinal cord in 20 healthy men and women. Functional connectivity was observed to vary between specific regions across painful and innocuous conditions. However, the same variations were not observed in the period of anticipation prior to the onset of stimulation. Specific connections varied with individual pain scores only during the noxious stimulation condition, indicating a significant role of individual differences in the experience of pain which are distinct from that of innocuous sensation. The results also illustrate significant differences in descending modulation before and during stimulation in both conditions. These findings contribute to a deeper understanding of the mechanisms underlying pain processing at the level of the brainstem and spinal cord, and how pain is modulated.