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Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.
We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).
We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.
This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Gender is a highly salient and important social group that shapes how children interact with others and how they are treated by others. In this Element, we offer an overview and review of the research on gender development in childhood from a developmental science perspective. We first define gender and the related concepts of sex and gender identity. Second, we discuss how variations in cultural context shape gender development around the world and how variations within gender groups add to the complexity of gender identity development. Third, we discuss major theoretical perspectives in developmental science for studying child gender. Fourth, we examine differences and similarities between girls and boys using the latest meta-analytic evidence. Fifth, we discuss the development of gender, gender identity, and gender socialization throughout infancy, early childhood, and middle childhood. We conclude with a discussion of future directions for the study of gender development in childhood.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Introduction: Paramedics commonly administer intravenous dextrose to severely hypoglycemic patients. Typically, the treatment provided is a 25g ampule of 50% dextrose (D50). This dose of D50 is meant to ensure a return to consciousness. However, this dose may be unnecessary and lead to harm or difficulties regulating blood glucose post treatment. We hypothesize that a lower dose such as dextrose 10% (D10) or titrating the D50 to desired level of consciousness may be optimal and avoid adverse events. Methods: We systematically searched Medline, Embase, CINAHL and Cochrane Central on June 5th 2019. PRISMA guidelines were followed. The GRADE methods and risk of bias assessments were applied to determine the certainty of the evidence. We included primary literature investigating the use of intravenous dextrose in hypoglycemic diabetic patients presenting to paramedics or the emergency department. Outcomes of interest were related to the safe and effective reversal of symptoms and blood glucose levels (BGL). Results: 660 abstracts were screened, 40 full text articles, with eight studies included. Data from three randomized controlled trials and five observational studies were analyzed. A single RCT comparing D10 to D50 was identified. The primary significant finding of the study was an increased post-treatment glycemic profile by 3.2 mmol/L in the D50 group; no other outcomes had significant differences between groups. When comparing pooled data from all the included studies we find higher symptom resolution in the D10 group compared to the D50 group; at 99.8% and 94.9% respectively. However, the mean time to resolution was approximately 4 minutes longer in the D10 group (4.1 minutes (D50) and 8 minutes (D10)). There was more need for subsequent doses in the D10 group at 23.0% versus 16.5% in the D50 group. The post treatment glycemic profile was lower in the D10 group at 5.9 mmol/L versus 8.5 mmol/L in the D50 group. Both treatments had nearly complete resolution of hypoglycemia; 98.7% (D50) and 99.2% (D10). No adverse events were observed in the D10 group (0/871) compared to 12/133 adverse events in the D50 group. Conclusion: D10 may be as effective as D50 at resolving symptoms and correcting hypoglycemia. Although the desired effect can take several minutes longer there appear to be fewer adverse events. The post treatment glycemic profile may facilitate less challenging ongoing glucose management by the patients.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Introduction: The Prehospital Evidence-based Practice (PEP) program is an online, freely accessible, continuously updated repository of appraised EMS research evidence. This report is an analysis of published evidence for EMS interventions used to assess and treat patients suffering from hypoglycemia. Methods: PubMed was systematically searched in June 2019. One author screened titles, abstracts and full-texts for relevance. Trained appraisers reviewed full text articles, scored each on a three-point Level of Evidence (LOE) scale (based on study design and quality) and three-point Direction of Evidence (DOE) scale (supportive, neutral, or opposing findings for each intervention's primary outcome), abstracted the primary outcome, setting and assigned an outcome category (patient or process). Second party appraisal was conducted for all included studies. The level and direction of each intervention was plotted in an evidence matrix, based on appraisals. Results: Twenty-nine studies were included and appraised for seven interventions: 5 drugs (Dextrose 50% (D50), Dextrose 10% (D10), glucagon, oral glucose and thiamine), one assessment tool (point-of-care (POC) glucose testing) and one call disposition (treat-and-release). The most frequently reported study primary outcomes were related to: clinical improvement (n = 15, 51.7%), feasibility/safety (n = 8, 27.6%), and diagnostics (n = 6, 20.7%). The majority of outcomes were patient focused (n = 18, 62.0%). Conclusion: EMS interventions for treating hypoglycemia are informed by high-quality supportive evidence. Both D50 and D10 are supported by high-quality evidence; suggesting D10 may be an effective alternative to the standard D50. “Treat-and-release” practices for hypoglycemia are supported by moderate-quality evidence for the patient related outcomes of relapse, patient preference and complications. This body of evidence is high-quality, patient-focused and conducted in the prehospital setting thus generalizable paramedic practice.