Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BACKGROUND: Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging. METHODS: We conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed. FINDINGS: 1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care). INTERPRETATION: In women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging. FUNDING: Barts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund.

Using propensity score matching to estimate treatment effects of afterschool programs on third-grade reading outcomes.

Evidence on whether afterschool programs enhance academic achievement is limited and mixed. In this study, a group of community providers delivered interventions to students to improve academic achievement. We used propensity score matching to estimate the impact of these afterschool interventions on third-grade reading achievement. A significant effect of moderate magnitude was found favoring students who participated in afterschool programming. Propensity score matching and other methodological considerations are described to support the importance and value of conducting rigorous evaluations of afterschool programs.

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial.

BACKGROUND: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. METHODS: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. RESULTS: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. CONCLUSIONS: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.

Practical implementation science: developing and piloting the quality implementation tool.

According to the Interactive Systems Framework for Dissemination and Implementation, implementation is a major mechanism and concern in bridging research and practice. The growing number of implementation frameworks need to be synthesized and translated so that the science and practice of quality implementation can be furthered. In this article, we: (1) use the synthesis of frameworks developed by Meyers et al. (Am J Commun Psychol, 2012) and translate the results into a practical implementation science tool to use for improving quality of implementation (i.e., the Quality Implementation Tool; QIT), and (2) present some of the benefits and limitations of the tool by describing how the QIT was implemented in two different pilot projects. We discuss how the QIT can be used to guide collaborative planning, monitoring, and evaluation of how an innovation is implemented.

The premises is the premise: understanding off- and on-premises alcohol sales outlets to improve environmental alcohol prevention strategies.

Environmental strategies to prevent the misuse of alcohol among youth--e.g., use of public policies to restrict minors' access to alcohol--have been shown to reduce underage drinking. However, implementation of policy changes often requires public and private partnerships. One way to support these partnerships is to better understand the target of many of the environmental strategies, which is the alcohol sales outlet. Knowing more about how off-premises outlets (e.g., liquor and convenience stores) and on-premises outlets (e.g., bars and restaurants) are alike and different could help community-based organizations better tailor, plan, and implement their environmental strategies and strengthen partnerships between the public and commercial sectors. We conducted a survey of managerial or supervisory staff and/or owners of 336 off- and on-premises alcohol outlets in six counties in South Carolina, comparing these two outlet types on their preferences regarding certain alcohol sales practices, beliefs toward underage drinking, alcohol sales practices, and outcomes. Multilevel logistic regression showed that while off- and on-premises outlets did have many similarities, off-premises outlets appear to engage in more practices designed to prevent sales of alcohol to minors than on-premises outlets. The relationship between certain Responsible Beverage Service (RBS) practices and outcomes varied by outlet type. This study furthers the understanding of the differences between off- and on-premises alcohol sales outlets and offers options for increasing and tailoring environmental prevention efforts to specific settings.

Hypothermia and targeted temperature management in cats and dogs.

OBJECTIVE: To review current knowledge surrounding the effects, treatment, and prognosis of hypothermia in people, dogs, and cats, as well as the application of therapeutic hypothermia in clinical medicine. ETIOLOGY: Hypothermia may be a primary or secondary condition, and may be due to environmental exposure, illness, medications, anesthesia, or trauma. Hypothermia has been applied therapeutically in human medicine for a variety of conditions, including postcardiac arrest. In veterinary medicine, the technique has been applied in cardiac surgeries requiring bypass and in a patient with intractable seizures. DIAGNOSIS: Hypothermia can be diagnosed based on presenting temperature or clinical signs, and appropriate diagnosis may require nontraditional thermometers. THERAPY: Rewarming is the primary treatment for accidental hypothermia, with intensity ranging from passive surface rewarming to extracorporeal rewarming. The goal is to return the core temperature to a level that restores normal physiologic function of all body processes. Other supportive therapies such as intravenous fluids are typically indicated, and if cardiopulmonary arrest is present, prolonged resuscitation may be required. In cases of secondary hypothermia, reversal of the underlying cause is important. PROGNOSIS: There are few prognostic indicators in human and veterinary patients with hypothermia. Even the most severely affected individuals, including those presenting in cardiopulmonary arrest, have potential for complete recovery with appropriate therapy. Therapeutic hypothermia has been shown to improve outcome in people following cardiac arrest. Further studies are needed to examine this application in veterinary medicine, as well as appropriate therapy and prognosis for cases of spontaneous hypothermia.