Requests, Issuing, and Hospital Admissions Regarding Mental Health Warrants Before and During the COVID-19 Pandemic in a Region in Portugal.

INTRODUCTION: Mental health warrants exist in most countries and are issued when patients have severe mental illness, refuse treatment, and present a serious risk to themselves or others. We describe the epidemiology of mental health warrant requests received, and warrants issued by a Public Health Unit in a Portuguese region, as well as subsequent hospital admissions before and during the COVID-19 pandemic. METHODS: We used routine administrative data of mental health warrant request entries from a Public Health Unit serving a population of 219 739 individuals and compared the average of monthly requests, issued warrants, and hospital admissions during two separate periods (January 2013 to January 2021 and February 2021 to October 2022) as well as the proportion of warrants issued, hospital admissions among requests, and other patient characteristics. We identified factors associated with hospital admissions among the requests using logistic regression. RESULTS: Monthly average warrant requests, issued warrants and hospital admissions increased after February 2021 (x̄ 2.87 vs 7.09 p < 0.001; x̄ 2.67 vs 6.42 p < 0.001; x̄ 1.55 vs 3.58 p < 0.001). We found no differences by period in the proportion of requests with issued warrants (92.8% vs 90.6% p = 0.42) nor the proportion of requests with subsequent hospital admissions (54.0% vs 49.0% p = 0.33). In the second period, there were differences in the proportion of patients with a previously diagnosed mental health disorder (95.3% vs 90.4% p = 0.049). There were significant differences in the distribution of the origin of requests. Being unemployed (OR:2.5 CI:1.2 - 5.2), not having completed high school (OR:2.01 CI:1.12 - 3.77) and having university education (OR:3.67 CI:1.27 - 10.57) degree were associated with hospital admission. CONCLUSION: Severe mental illness with criteria for mental health warrants may require more resources and different approaches due to a possible increase during and after the COVID-19 pandemic. Community based mental healthcare, incentivized follow-up by primary care and ambulatory treatment may be considered. Further research should evaluate both the national and international trends and associated factors.

The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes.

This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1 rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.

The needs of children receiving end of life care and the impact of a paediatric palliative care team: a retrospective cohort study.

Published data collected in hospital during the last year of life of children with life-limiting complex chronic conditions (CCC) is scarce, yet critical, for the implementation of paediatric palliative care (PPC). This study aims to describe the last year of life of children with CCC, in terms of clinical characteristics, hospital resources and the impact of referral to a hospital-based PPC team (PPCT). Using a retrospective cohort study, we examined the clinical records of children aged 1-18 years of age with CCC who died in a tertiary hospital between January 2016 and December 2020. Hospital resources utilised in the last year of life, therapies and procedures during the final week of life, decision to limit treatment (DLT), referral to the PPCT and place of death were analysed. Seventy-two patients (60% male) with a median age of 10.1 years were included. Most had ≥ 2 CCC (58%) with cancer as the most common diagnosis (47%). The group with ≥ 3 CCC (n = 23) had longer hospital stays (p = 0.041). Of the 17 patients referred to the PPCT, there was a higher frequency of DLT (94% vs. 40% in non-referred, p < 0.001), greater use of subcutaneous route (53% vs. 0%, p < 0.001), lower frequency of blood transfusions (12% vs. 55%, p = 0.002) and a lower proportion of deaths in the Intensive Care Unit (6% vs. 64%, p < 0.001). CONCLUSIONS: Early implementation of PPC optimises the use of hospital resources, minimises invasive procedures and therapies, and may develop effective and sustainable alternatives which are better suited to the needs of children and families. WHAT IS KNOWN: • In recent years, there has been an increased prevalence of complex chronic condition (CCC), which has led to more specialised and prolonged medical care until the end of life. • There are few paediatric studies on use of hospital resources and the invasiveness of procedures in the last year of life for children. WHAT IS NEW: • This study is one of the few to provide a comprehensive characterisation of the last year of life of children/adolescents with CCC. • Timely referral to a specialised PPC team optimises the use of hospital resources, minimise invasive procedures and develop effective and sustainable alternatives which are better suited to the needs of children and/or families.

IL6-174G > C genetic polymorphism influences antidepressant treatment outcome.

BACKGROUND: Major depressive disorder is a condition associated with dysregulated cytokine levels; among these, IL6. Furthermore, genetic variations within cytokine genes have been proposed to predict antidepressant treatment outcome. OBJECTIVES: This study aims to evaluate the role of IL6-174G > C and IL6R D358A A > C functional polymorphisms in antidepressant treatment phenotypes, specifically remission, relapse, and treatment resistant depression (TRD). METHODS: The referred polymorphisms were genotyped in 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. RESULTS: It was found that patients carrying IL6-174 GC genotype present a protection towards the development of TRD (OR = 0.242; 95% CI = 0.068-0.869; p = .038), when compared with GG genotype. Additionally, carriers of IL6-174 CC genotype remit earlier than patients with IL6-174 GG/GC genotypes, with a median time to remission of 6 weeks for CC carriers and 15 weeks for GG or GC carriers (p = .030, Log-rank test). No association was found between IL6R D358A genetic polymorphism and any of the treatment phenotypes evaluated. CONCLUSIONS: The IL6-174G > C polymorphism influences antidepressant treatment outcome in this sub-set of MDD patients, providing a putative mechanistic link for the dysregulated IL-6 levels described in the literature in patients with TRD.

The role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes: A preliminary report.

Recent studies suggest that immune activation and cytokines, such as IL-18, are involved in depression. IL-18 is expressed in brain and is increased in patients with moderate to severe depression. In this study we aim to evaluate the role of IL18-607C>A and IL18-137G>C promoter polymorphisms in antidepressant treatment phenotypes, specifically relapse and treatment resistant depression (TRD). We genotyped the referred polymorphisms in a subset of 80 MDD patients followed at Hospital Magalhães Lemos, Portugal, within a period of 27 months. Patients carrying IL18-607 CA or AA genotypes were significantly more prone to relapse after AD treatment and present a significantly lower time to relapse than patients carrying CC genotype. Similarly, patients carrying IL18-137 GC or CC genotypes have a significantly higher risk of relapse and display relapse significantly earlier than the ones carrying GG genotype. Due to the low number of IL18-607 CC and IL18-137 GG in the relapse subgroup (n=3 and n=5, respectively), results were validated by bootstrapping analysis, and remained significant. No association was found between the evaluated genetic polymorphisms and TRD. IL18 peripheral mRNA levels were upregulated in IL18-607 CA or AA carriers. This preliminary report indicates that IL18-607C>A and IL18-137G>C genetic polymorphisms seem to influence depression relapse after antidepressant treatment in our subset of depressed patients, and may possibly contribute to the disregulated IL-18 levels found in patients with depression.

FAS -670A>G genetic polymorphism Is associated with Treatment Resistant Depression.

BACKGROUND: Hippocampal neurogenesis has been suggested as a downstream event of antidepressants (AD) mechanism of action and might explain the lag time between AD administration and the therapeutic effect. Despite the widespread use of AD in the context of Major Depressive Disorder (MDD) there are no reliable biomarkers of treatment response phenotypes, and a significant proportion of patients display Treatment Resistant Depression (TRD). Fas/FasL system is one of the best-known death-receptor mediated cell signaling systems and is recognized to regulate cell proliferation and tumor cell growth. Recently this pathway has been described to be involved in neurogenesis and neuroplasticity. METHODS: Since FAS -670A>G and FASL -844T>C functional polymorphisms never been evaluated in the context of depression and antidepressant therapy, we genotyped FAS -670A>G and FASL -844T>C in a subset of 80 MDD patients to evaluate their role in antidepressant treatment response phenotypes. RESULTS: We found that the presence of FAS -670G allele was associated with antidepressant bad prognosis (relapse or TRD: OR=6.200; 95% CI: [1.875-20.499]; p=0.001), and we observed that patients carrying this allele have a higher risk to develop TRD (OR=10.895; 95% CI: [1.362-87.135]; p=0.008). Moreover, multivariate analysis adjusted to potentials confounders showed that patients carrying G allele have higher risk of early relapse (HR=3.827; 95% CI: [1.072-13.659]; p=0.039). FAS mRNA levels were down-regulated among G carriers, whose genotypes were more common in TRD patients. No association was found between FASL-844T>C genetic polymorphism and any treatment phenotypes. LIMITATIONS: Small sample size. Patients used antidepressants with different mechanisms of action. CONCLUSION: To the best of our knowledge this is the first study to evaluate the role of FAS functional polymorphism in the outcome of antidepressant therapy. This preliminary report associates FAS -670A>G genetic polymorphism with Treatment Resistant Depression and with time to relapse. The current results may possibly be given to the recent recognized role of Fas in neurogenesis and/or neuroplasticity.

An association between temporomandibular disorder and gum chewing.

This single center, randomized, small study sought to investigate the prevalence and frequency of chewing gum consumption, and whether there is a relationship between these factors and the presence of symptoms associated with temporomandibular disorder (TMD). Subjects were divided into 7 groups based on their parafunctional oral habits. Of these, subjects who chewed gum were divided into 5 subgroups (A-E) based on their gum chewing habits. Group A chewed gum <1 hour/day (n = 12), Group B chewed gum 1-2 hours/day (n = 11), Group C chewed gum 3 hours/day (n = 6), and Group D chewed gum >3 hours at a time (n = 8); the frequency of gum chewing in Groups A-D was once a week. Group E subjects chewed gum 1-3 times/week for at least 1 hour each occurrence (n = 2). Sixty-three percent of the subjects in Group D reported TMD symptoms of arthralgia and myofascial pain. Thirty-three percent of the subjects in Group C showed symptoms of arthralgia. Eighty-three percent of the subjects in Group A and 27% in Group B reported myofascial pain. All subjects in Group E reported masseter hypertrophy. The remaining 2 groups were Group F, subjects that didn't chew gum but had other parafunctional oral habits (n = 2), and Group G, subjects who didn't have parafunctional oral habits (n = 12).

Common genetic polymorphisms in the ABCB1 gene are associated with risk of major depressive disorder in male Portuguese individuals.

Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.