Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials.

INTRODUCTION: Self-monitoring of blood pressure (BP) in pregnancy could improve the detection and management of pregnancy hypertension, while also empowering and engaging women in their own care. Two linked trials aim to evaluate whether BP self-monitoring in pregnancy improves the detection of raised BP during higher risk pregnancies (BUMP 1) and whether self-monitoring reduces systolic BP during hypertensive pregnancy (BUMP 2). METHODS AND ANALYSES: Both are multicentre, non-masked, parallel group, randomised controlled trials. Participants will be randomised to self-monitoring with telemonitoring or usual care. BUMP 1 will recruit a minimum of 2262 pregnant women at higher risk of pregnancy hypertension and BUMP 2 will recruit a minimum of 512 pregnant women with either gestational or chronic hypertension. The BUMP 1 primary outcome is the time to the first recording of raised BP by a healthcare professional. The BUMP 2 primary outcome is mean systolic BP between baseline and delivery recorded by healthcare professionals. Other outcomes will include maternal and perinatal outcomes, quality of life and adverse events. An economic evaluation of BP self-monitoring in addition to usual care compared with usual care alone will be assessed across both study populations within trial and with modelling to estimate long-term cost-effectiveness. A linked process evaluation will combine quantitative and qualitative data to examine how BP self-monitoring in pregnancy is implemented and accepted in both daily life and routine clinical practice. ETHICS AND DISSEMINATION: The trials have been approved by a Research Ethics Committee (17/WM/0241) and relevant research authorities. They will be published in peer-reviewed journals and presented at national and international conferences. If shown to be effective, BP self-monitoring would be applicable to a large population of pregnant women. TRIAL REGISTRATION NUMBER: NCT03334149.This work is funded from a National Institute for Health Research (NIHR) Programme grant for applied research (RP-PG- 1209-10051) and an NIHR Professorship awarded to RJM (NIHR-RP- R2- 12-015). RJM and KLT receive funding from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. JS is a National Institute for Health Research (NIHR) Senior Investigator and supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London (NIHR CLAHRC South London) at King’s College Hospital NHS Foundation Trust. Service support costs will be administered through the NIHR Clinical Research Network

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

The Use of Silgel STC-SE, a Topical Silicone Gel for the Treatment and Reduction of Hypertrophic and Keloid Scars

Upper west wall covered in hundreds of tiny Buddhas; The Yungang Grottoes are located 16 km west of Datong and comprise about 53 caves and 51,000 statues. The site stretches about 1 kilometer from east to west and was hollowed from the sandstone cliffs of the Wuzhou Mountains during the 5th century CE under the patronage of the Northern Wei dynasty. Founded by the Tuoba or Toba people, who ruled northern China during the Northern and Southern Dynasties period (310-589 CE), the Wei dynasty adopted Buddhism as its state religion. Work was begun at Yungang by the emperor Wenchengdi (reigned 452-465). The caves range in width from 23 m to a few metres. In 494, the Wei moved their capital from Datong to Luoyang and the Yungang Grottoes slowly fell into decay. The Grottoes have been a UNESCO World Heritage site since 2001. Cave 15 is badly eroded but still contains thousands of tiny Buddhas carved into the walls, hence the popular name of the cave. Source: Grove Art Online; http://www.oxfordartonline.com/ (accessed 5/9/2011

Critical distance : how a mental health arts and film festival makes audiences think

This article draws on the views of audiences who attended the Scottish Mental Health Arts & Film Festival of 2010 and examines the impact of the festival on audiences' perceptions regarding the arts and mental health. Structured exit interviews were conducted with 53 festival attendees, immediately following festival events at a variety of arts venues. A number of themes were extracted from the interview transcripts via thematic analysis. These themes underscore the utility of the arts for exploring issues pertaining to mental health. For example, interviewees commented on how the arts could be applied to working practice in mental health, and described the gains afforded from sharing personal experiences of mental health through art. Themes regarding the arts' potential for encouraging reflective thinking and changing attitudes were also noted, with particular reference being made to stigma and mental health. The limitations of the study are discussed, alongside future directions for similar research on the impact of cultural activities for social change. Presenting an arts programme that is themed without being message-laden can impact on thinking around mental health that is more empathetic and understanding

Effect of self-monitoring of blood pressure on diagnosis of hypertension during higher-risk pregnancy:: The BUMP 1 randomized trial

Importance: Inadequate management of elevated BP is a significant contributing factor to maternal deaths. Self-monitoring of blood pressure (BP) in the general population has been shown to improve the diagnosis and management of hypertension, however little is known about its use in pregnancy. Objective: To determine whether self-monitoring of BP in higher risk pregnancies leads to earlier detection of pregnancy hypertension.Design, setting and participants: Unmasked, randomised clinical trial that recruited between November 2018 and October 2019. 2441 pregnant individuals at higher risk of pre-eclampsia were recruited at 20 weeks’ gestation from 15 hospital maternity units in England with final follow-up in April 2020.Interventions: Participating individuals were randomised to either BP self-monitoring with telemonitoring (n=1223) plus usual care or usual antenatal care alone (n=1218) without access to telemonitored BP.Main Outcomes: The primary outcome was time to first recorded hypertension measured by a healthcare professional.Results: Among 2441 participants who were randomized (mean age, 33; median gestation 20 weeks), 2346 (96%) completed the trial. The time from randomisation to clinic recording of hypertension was not significantly different between individuals in the self-monitoring group (mean 104 days) vs the usual care group (mean 106 days) (mean difference -1.6 days (95% confidence intervals -8.1, 4.9, p = 0.6). Eighteen serious adverse events were reported during the trial with none judged as related to the intervention: 12 (1%) in the self-monitoring group and 6 (0.5%) in those receiving usual care.Conclusions and relevance: Among pregnant individuals at higher risk of pre-eclampsia, blood pressure self-monitoring with telemonitoring compared with usual care did not lead to significantly earlier clinic-based detection of hypertension.Trial Registration: ClinicalTrials.gov NCT03334149 https://clinicaltrials.gov/ct2/show/NCT0333414

Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals with Chronic or Gestational Hypertension:The BUMP 2 Randomized Clinical Trial

Importance Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks’ gestation) or with gestational hypertension (enrolled between 20 and 37 weeks’ gestation). Final follow-up was in May 2020. Interventions Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, −1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, −0.03 mm Hg [95% CI, −2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration ClinicalTrials.gov Identifier: NCT0333414

Effect of self-monitoring of blood pressure on blood pressure control in pregnant individuals with chronic or gestational hypertension: the BUMP 2 randomized trial

Importance Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks’ gestation) or with gestational hypertension (enrolled between 20 and 37 weeks’ gestation). Final follow-up was in May 2020. Interventions Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, −1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, −0.03 mm Hg [95% CI, −2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration ClinicalTrials.gov Identifier: NCT03334149</p

POSEIDON trial phase 1B results : Safety, efficacy and circulating tumor DNA response of the beta isoform-sparing PI3K inhibitor taselisib (GDC-0032) combined with tamoxifen in hormone receptor positive metastatic breast cancer patients

Purpose: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)–positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform–sparing PI3 kinase inhibitor. Patients and Methods: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. Results: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. Conclusions: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting