Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies

Multinational Experiences in Reducing and Preventing the Use of Restraint and Seclusion

Restraint and seclusion (R/S) have been used in many countries and across service sectors for centuries. With the recent and increasing recognition of the harm associated with these procedures, efforts have been made to reduce and prevent R/S. Following a scathing media exposé in 1998 and congressional scrutiny, the United States began a national effort to reduce and prevent R/S use. With federal impetus and funding, an evidence-based practice, the Six Core Strategies1 to Prevent Conflict, Violence and the Use of Seclusion and Restraint, was developed. This model was widely and successfully implemented in a number of U.S. states and is being adopted by other countries, including Finland, Australia, and the United Kingdom. Recently, the first cluster randomized controlled study of the Six Core Strategies in Finland provided the first evidence-based data of the safety and effectiveness of a coercion prevention methodology. Preliminary findings of some of the international efforts are discussed. Reduction in R/S use and other positive outcomes are also reported

Looking after bubba for all our mob: Aboriginal and Torres Strait Islander community experiences and perceptions of stillbirth

The stillbirth rate among Aboriginal and Torres Strait Islander women and communities in Australia is around double that of non-Indigenous women. While the development of effective prevention strategies during pregnancy and improving care following stillbirth for women and families in communities has become a national priority, there has been limited progress in stillbirth disparities. With community permission, this study aimed to gain a better understanding of community experiences, perceptions, and priorities around stillbirth. We undertook an Indigenous researcher-led, qualitative study, with community consultations guided by a cultural protection protocol and within an unstructured research framework. A total of 18 communities were consulted face-to-face through yarning interviews, focus groups and workshops. This included 54 community member and 159 health professional participants across remote, regional, and urban areas of Queensland, Western Australia, Victoria, South Australia, and Northern Territory. Thematic analysis of consultation data identified common themes across five focus/priority areas to address stillbirth: Stillbirth or Sorry Business Baby care needs to be family-centered; using Indigenous “ways of knowing, being, and doing” to ensure cultural safety; application of Birthing on Country principles to maternal and perinatal care; and yarning approaches to improve communication and learning or education. The results underscore the critical need to co-design evidence-based, culturally appropriate, and community-acceptable resources to help reduce existing disparities in stillbirth rates

Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership

This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Characterisation of musculoskeletal interactions after spinal cord injury

A well-established principle called Wolff's Law asserts that the changes in form and/or function of bone are followed by changes in its internal architecture (Frost 1994). Bone is adaptive, and its strength is dependent on its mechanical loading history. The largest loads imposed on bones are generally the result of muscular contraction (Lu et al. 1997), and thus bone adaptation is strongly linked with muscle activity. Following a complete spinal cord injury (SCI), paralysis of the lower limbs leads to rapid muscle atrophy. In time, this is followed by bone loss due to the extreme reduction in mechanical loading on the previously weight-bearing bones of the lower limbs. This research project aimed to study how early muscle atrophy could be used to predict future bone loss. Eighteen subjects with motor complete SCI were scanned using peripheral quantitative computed tomography (pQCT) at the 66% distal tibia at four separate time intervals within the first year following injury. Fully automated software was then developed which was able to segment the tissues within each scan, ultimately determining the quantities of fat, muscle, and bone. From these data, changes in tissue volume could be characterised for individual subjects. Over 12 months, fat increased by 39:2% ± 42:4, muscle decreased by 4:4% ± 17:3, and cortical bone decreased by 2:5% ± 2:3. The data further revealed that there was a positive, but weak, correlation between change in muscle CSA at 4 months post-SCI and change in cortical bone CSA at 12 months post-SCI (r = 0:27) when compared to the baseline scan; however, this value was not statistically significant. These results suggest that there may be a relationship between early muscle atrophy and future bone loss. However, future work in this area must be accomplished to support this theory.A well-established principle called Wolff's Law asserts that the changes in form and/or function of bone are followed by changes in its internal architecture (Frost 1994). Bone is adaptive, and its strength is dependent on its mechanical loading history. The largest loads imposed on bones are generally the result of muscular contraction (Lu et al. 1997), and thus bone adaptation is strongly linked with muscle activity. Following a complete spinal cord injury (SCI), paralysis of the lower limbs leads to rapid muscle atrophy. In time, this is followed by bone loss due to the extreme reduction in mechanical loading on the previously weight-bearing bones of the lower limbs. This research project aimed to study how early muscle atrophy could be used to predict future bone loss. Eighteen subjects with motor complete SCI were scanned using peripheral quantitative computed tomography (pQCT) at the 66% distal tibia at four separate time intervals within the first year following injury. Fully automated software was then developed which was able to segment the tissues within each scan, ultimately determining the quantities of fat, muscle, and bone. From these data, changes in tissue volume could be characterised for individual subjects. Over 12 months, fat increased by 39:2% ± 42:4, muscle decreased by 4:4% ± 17:3, and cortical bone decreased by 2:5% ± 2:3. The data further revealed that there was a positive, but weak, correlation between change in muscle CSA at 4 months post-SCI and change in cortical bone CSA at 12 months post-SCI (r = 0:27) when compared to the baseline scan; however, this value was not statistically significant. These results suggest that there may be a relationship between early muscle atrophy and future bone loss. However, future work in this area must be accomplished to support this theory