Data for Thinking Healthy Programme India trial (THPP-India)

An anonymised dataset of 280 women (one row per woman) who gave informed consent to participate in an individually-randomised, parallel, superiority, controlled trial in Goa, India in 2014-2016. The intervention was an adapted version of the Thinking Healthy Programme, delivered by peers; the control was enhanced usual care. Further details are available in the published protocol and paper. The dataset contains records of variables on stratified randomisation, socio-demographic information, depression and related outcomes, and therapy adherence. Visits occurred at baseline, and 3 and 6 months post-natal

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

A qualitative analysis of relatives', health professionals' and service users' views on the involvement in care of relatives in Bipolar Disorder

Background: Relatives of people with bipolar disorder report that services do not meet their own needs, despite clinical recommendations for the development of care plans for relatives, provision of information regarding their statutory entitlements, and formal involvement in decision making meetings. Further, there is now conclusive evidence highlighting the benefits of relatives' involvement in improving outcomes for service users, relatives, and the health system as a whole. This qualitative study explored the views of relatives of people with bipolar disorder, service users and healthcare professionals regarding the barriers and the facilitators to relatives' involvement in care. Methods: Thirty five people were interviewed (12 relatives, 11 service users and 12 healthcare professionals). Audio recordings were transcribed verbatim and common themes in participants' narratives emerged using framework analysis. Results: Participants' accounts confirmed the existence of opportunities for relatives to be involved. These, however, were limited and not always accessible. There were three factors identified that influenced accessibility namely: pre-existing worldviews, the quality of relationships and of communication between those involved, and specific structural impediments. Discussion: These themes are understood as intertwined and dependent on one another. People's thoughts, beliefs, attitudes, cultural identifications and worldviews often underlie the ways by which they communicate and the quality of their relationship. These, however, need to be conceptualised within operational frameworks and policy agendas in health settings that often limit bipolar relatives' accessibility to opportunities for being more formally involved. Conclusions: Involving relatives leads to clear benefits for relatives, service users, healthcare professionals, and the health system as a whole. Successful involvement of relatives, however, depends on a complex network of processes and interactions among all those involved and requires strategic planning from policy makers, operational plans and allocation of resources

Changes in clinical disease activity are weakly linked to changes in MRI inflammation on treat-to-target escalation of therapy in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) treat-to-target (T2T) regimens often use the disease activity score (28 joints) incorporating C-reactive protein (DAS28CRP) as an outcome measure. We compared changes in the DAS28CRP with changes in magnetic resonance imaging (MRI) inflammation on treatment escalation. Methods Eighty seropositive RA patients with active disease were enrolled. Group A (N = 57) escalated to another conventional disease-modifying therapy (cDMARD) combination, and Group B (N = 23) to anti-TNF therapy/cDMARDs. Contrast-enhanced 3T-MRI wrist scans were obtained before and 4 months after regimen change. Scan pairs were scored for inflammation (MRI(i)) and damage. Disease activity was assessed using the DAS28CRP. Results Eighty patients were enrolled and 66 MRI scan pairs were available for analysis. Intra-reader reliability was high: intraclass correlation coefficient (average) 0.89 (0.56–0.97). ΔDAS28CRP did not differ between groups: Group A, −0.94 (−3.30, 1.61); Group B, −1.53 (−3.59, 0.56) (p = 0.45). ΔMRI(i) also did not differ: Group A, 0 (−25, 10); Group B, −1 (−15, 28) (p = 0.12). Combining groups, ΔMRI(i) correlated weakly with ΔDAS28CRP (Spearman’s 0.36, p = 0.003). Using multiple linear regression analysis adjusting for confounders, ΔDAS28CRP was associated with ΔMRI(i) (p = 0.056). Of the individual MRI measures, only Δtenosynovitis correlated with ΔDAS28CRP (Spearman’s 0.33, p = 0.007). ΔMRI(i) was negatively associated with the MRI erosion score at entry (p = 0.0052). Conclusions We report the first study investigating the link between changes in clinical and imaging inflammation in a real-world RA cohort escalating to conventional and biologic DMARDs. The association was significant but relatively weak, suggesting that MRI targets cannot yet be advocated as outcomes for T2T escalation. Trial registration ANZCTR 12614000895684 . Registered 22 August 2014

Sperm Chromatin Immaturity Observed in Short Abstinence Ejaculates Affects DNA Integrity and Longevity <i>In Vitro</i>

<div><p>Background</p><p>The influence of ejaculatory abstinence (EA) on semen parameters and subsequent reproductive outcome is still debatable; hence understanding the impact of EA on sperm structural and functional integrity may provide a valuable information on predicting successful clinical outcome.</p><p>Objective</p><p>To understand the influence of EA on sperm chromatin maturity, integrity, longevity and global methylation status.</p><p>Methods</p><p>This experimental prospective study included 76 ejaculates from 19 healthy volunteers who provided ejaculates after observing 1, 3, 5 and 7 days of abstinence. Sperm chromatin maturity, DNA integrity and global methylation status were assessed in the neat ejaculate. Sperm motility, DNA integrity and longevity were assessed in the processed fraction of the fresh and frozen-thawed ejaculates to determine their association with the length of EA.</p><p>Results</p><p>Spermatozoa from 1 day ejaculatory abstinence (EA-1) displayed significantly higher level of sperm chromatin immaturity in comparison to EA-3 (P < 0.05) and EA-5 (P < 0.01) whereas; the number of 5-methyl cytosine immunostained spermatozoa did not vary significantly across groups. On the other hand, <i>in vitro</i> incubation of processed ejaculate from EA-1 resulted in approximately 20 and 40 fold increase in the DNA fragmented spermatozoa at the end of 6 and 24h respectively (P < 0.01–0.001).</p><p>Conclusion</p><p>Use of short-term EA for therapeutic fertilization would be a clinically valuable strategy to improve the DNA quality. However, use of such spermatozoa after prolonged incubation <i>in vitro</i> should be avoided as it can carry a substantial risk of transmitting DNA fragmentation to the oocytes.</p></div

Basic semen characteristics in relation to different EA intervals.

<p>Basic semen characteristics in relation to different EA intervals.</p

Sperm motility and DNA fragmentation analysis in relation to EA.

<p>A) Sperm motility analysis in neat ejaculate (N = 76) (■) as well as in the processed fraction (N = 32) from four study intervals. Processed fraction was incubated at 37°C and motility analysis was performed at 0h (●), 6h (▲), and 24h (▼) time interval. Please note that differences in sperm motility with corresponding EA intervals were not statistically significant. B) Box plot depicting the DNA fragmentation level as measured by the sperm chromatin dispersion (SCD) assay in the neat ejaculate (N = 56) (□) and processed fraction (N = 32) (■). ^aP < 0.05 <i>Vs</i> corresponding group in EA-5; ^bP < 0.001 <i>Vs</i> corresponding group in EA-7; ^c P < 0.01 <i>Vs</i> corresponding group in EA-7; ^dP < 0.05 <i>Vs</i> corresponding group in EA-7. C) Sperm DNA longevity analysis by SCD assay in the processed fraction at 0h (■), 1h (●), 6h (▲), and 24h (▼) time interval.</p