Abstract
Introduction
A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term “mood instability” reflecting the variability in mood seems ...associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse.
During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment
including
clinical feedback versus (2) daily smartphone-based monitoring
without
clinical feedback or (3) daily smartphone-based mood monitoring
only
improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder.
Methods and analysis
The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment
including
a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring
without
a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial.
Ethics and dissemination
The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients’ organizations and media outlets.
Trial registration
Trial registration number: NCT04230421. Date March 1, 2021. Version 1.
Weathering of rocks takes place through complex processes involving an intimate coupling between mechanical disintegration of the rocks and interactions between the exposed rock surface, the ...hydrosphere and the biosphere. It is still poorly understood how this coupling affects weathering rates and patterns produced by weathering. Here, we show that the observed spheroidal weathering patterns in basaltic intrusions (dolerites) in the Karoo Basin in South Africa are created through volume expanding reactions which set up stresses that not only lead to spalling of spheroidal layers of rock, but also drive a large scale hierarchical fracturing process by which the dolerite is continuously undergoing domain division. The fracture processes generates new reactive surface area in a self-accelerating manner, thus providing a first-order control on the total weathering rate.
Subarachnoid haemorrhage (SAH) carries a high burden of morbidity and mortality. One in three patients develop vasospasm, which is associated with Delayed Cerebral Ischemia. The pathophysiology ...includes vasoconstrictor receptor upregulation in cerebral arteries. The protein kinase C – inhibitor RO-31-7549 reduces the expression of several vasoconstrictor receptors and normalizes cerebral blood flow in experimental SAH but functional and behavioural effects are unknown. This study was undertaken to analyse functional outcomes up to 14 days after experimental SAH.
54 male rats were randomised to experimental SAH or sham, using the pre-chiasmatic, single injection model, and subsequent treatment or vehicle. 42 remained for final analysis. The animals were euthanized on day 14 or when reaching a humane endpoint. The primary endpoint was overall survival, defined as either spontaneous mortality or when reaching a predefined humane endpoint. The secondary outcomes were differences in the rotating pole test, weight, open field test, novel object recognition and qPCR of selected inflammatory markers.
In the vehicle group 6/15 rats reached the humane endpoint of >20 % weight loss compared to 1/14 in the treatment group. This resulted in a significant reduced risk of early euthanasia due to >20 % weight loss of HR 0.15 (0.03–0.66, p = 0.04). Furthermore, the treatment group did significantly better on the rotating pole test, RR 0.64 (0.47–0.91, p = 0.02).
RO-31-7549 improved outcomes in terms >20 % weight loss and rotating pole performance after experimental SAH and could be investigated.
Treatment of postoperative pain should rely on results from randomized controlled trials and meta-analyses of high scientific quality. The efficacy of a particular intervention may depend on the type ...of surgical procedure, which supports the reporting of "procedure-specific" interventions. The aim of this systematic review was to document the procedure-specific evidence for analgesic interventions after total hip arthroplasty (THA). This PRISMA-compliant and PROSPERO-registered review includes randomized placebo-controlled trials (RCTs) of medication-based analgesic interventions after THA. Endpoints were postoperative opioid consumption, pain scores (rest and during mobilization), adverse events, and length of hospital stay. Fifty-eight trials with 19 different interventions were retrieved. High risk of bias, substantial differences in assessment-tools and criteria for pain, irregular reporting of adverse events, considerable differences in supplemental analgesic consumption, and basic analgesic regimens generally characterized trials. Meta-analyses of non-steroidal anti-inflammatory drugs, local infiltration analgesia, intrathecal opioids, and lumbar plexus block provided a 24-hour intravenous morphine-sparing effect of 14.1 (95 % confidence interval: 8.0-20.2) mg, 7.5 (3.7-11.3) mg, 19.8 (14.9-24.7) mg, and 11.9 (6.4-17.3) mg, respectively. Non-steroidal anti-inflammatory drugs and lumbar plexus block were demonstrated to provide reductions in postoperative pain scores. Intrathecal opioids increased pruritus, and lumbar plexus block reduced nausea and pruritus. The GRADE-rated quality of evidence ranged from low to very low throughout the analyses. This review demonstrated, that some analgesic interventions may have the capacity to reduce mean opioid requirements and/or mean pain intensity compared with controls, but the available randomized placebo-controlled trials does not allow a designation of a "best proven intervention" for THA.
Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple ...differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA.
To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle.
One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity.
Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.
Sufficient pain management is a necessity and can play an important role in patients’ contentment.
To investigate the instituted postoperative pain treatment, patients’ levels of pain, opioid ...consumption, and patient contentment, supplemented with a questionnaire based on the International Pain Outcome (IPO).
This prospective observational cohort study was conducted at Zealand University Hospital Køge, Denmark (ZUHK) from March 8, 2017, to January 7, 2019, aiming for a consecutive inclusion of 200 patients, 40 from five major surgical procedures. The study was approved by the Danish Data Protection Agency (REG-121-2016) and registered at ClinicalTrials.gov (NCT03080272). The Research Ethics Committee of the Zealand Region was consulted, but approval was not needed according to Danish law (J.nr. 16-000014).
We included 189 patients in total. We found a significant number of patients that did not achieve “no worse than mild pain” (Numeric Rating Scale ≤3) across surgical procedures. The provided pain treatment was heterogenic and inconsistent even among individuals who underwent similar surgical procedures. Although patients did not achieve “no worse than mild pain” (Numeric Rating Scale ≤3), the majority stated that they were content with their pain treatment.
The analgesic treatment varied between procedures and patients and a significant number of patients did not achieve “no worse than mild pain” (Numeric Rating Scale ≤3). A significant association between patient contentment and experience of severe pain, pain relief, and involvement in own pain treatment, was found.
Laparoscopic cholecystectomy is associated with postoperative pain of moderate intensity in the early postoperative period. Recent randomized trials have demonstrated the efficacy of transversus ...abdominis plane (TAP) block in providing postoperative analgesia after abdominal surgery. We hypothesized that a TAP block may reduce pain while coughing and at rest for the first 24 postoperative hours, opioid consumption, and opioid side effects in patients undergoing laparoscopic cholecystectomy in day-case surgery.
In this randomized, double-blind study, 80 patients undergoing laparoscopic cholecystectomy in our day-case surgery unit were allocated to receive either bilateral ultrasound-guided posterior TAP blocks (20 mL 0.5% ropivacaine) or placebo blocks. Postoperative pain treatment consisted of oral acetaminophen 1000 mg × 4, oral ibuprofen 400 mg × 3, IV morphine (0-2 hours postoperatively), and oral ketobemidone (2-24 hours postoperatively). The primary outcome was postoperative pain scores while coughing calculated as area under the curve for the first 24 postoperative hours (AUC/24 h). Secondary outcomes were pain scores at rest (AUC/24 h), opioid consumption, and side effects. Patients were assessed 0, 2, 4, 6, 8, and 24 hours postoperatively. Group-wise comparisons of visual analog scale (VAS) pain (AUC/24 h) were performed with the 2-sample t test. Morphine and ketobemidone consumption were compared with the Mann-Whitney test for unpaired data. Categorical data were analyzed using the χ(2) test.
The primary outcome variable, VAS pain scores while coughing (AUC/24 h), was significantly reduced in the TAP versus the placebo group (P = 0.04); group TAP: 26 mm (SD 13) (weighted average level) versus group placebo: 34 (18) (95% confidence interval): 0.5-15 mm). VAS pain scores at rest (AUC/24 h) showed no significant difference between groups. Median morphine consumption (0-2 hours postoperatively) was 7.5 mg (interquartile range: 5-10 mg) in the placebo group compared with 5 mg (interquartile range: 0-5 mg) in the TAP group (P < 0.001). The odds ratio of a random patient in group TAP having less morphine consumption than a random patient in group placebo was P (group TAP < group placebo) = 0.26 (confidence interval: 0.15, 0.37) where 0.5 represents no difference between groups. There were no between-group differences in total ketobemidone consumption, levels of nausea and sedation, number of patients vomiting, or consumption of ondansetron.
TAP block after laparoscopic cholecystectomy may have some beneficial effect in reducing pain while coughing and on opioid requirements, but this effect is probably rather small.
It has been argued that postoperative pain treatment should be "procedure-specific", since different analgesics may have specific effects dependent on the surgical procedure. The aim of the present ...subgroup analysis was to compare the beneficial and harmful effects of perioperative gabapentin treatment in different surgical procedures.
Relevant databases were searched for randomized clinical trials (RCTs) comparing gabapentin versus placebo. Two authors independently screened titles and abstracts, extracted data and assessed risk of bias. The primary outcomes were differences in 24-h morphine consumption, and serious adverse events (SAE) between surgical procedures. These subgroup analyses were predefined in a PRISMA compliant systematic review registered at PROSPERO (ID: CRD42013006538). It was predefined that conclusions should primarily be based on trials classified as overall low risk of bias.
Seventy-four RCTs with 5645 patients were included, assessing benefit and harm in cholecystectomy, hysterectomy, mastectomy, and arthroplasty surgery, spinal surgery, and thoracic surgery. Only eight of 74 trials were classified as overall low risk of bias limiting our ability to conclude on the estimates in most meta-analyses. The differences between surgical procedures in these trials were not statistically significant when tested for subgroup differences. Fifteen trials with 1377 patients reported a total of 59 SAEs, most of which were observed in the thoracic surgery group.
Both beneficial and harmful effects in these subgroup analyses were influenced by bias and insufficient data, limiting conclusions. With these limitations, we could not adequately test for differences in beneficial or harmful outcomes between six surgical subgroups undergoing perioperative gabapentin treatment.
PDF
