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Objective: The aim of this study was to examine modifiable mediators for socioeconomic disparities in childhood obesity in the United States.Methods: This study used the data of 1,211 mother-child dyads from a US national birth cohort from pregnancy to 6 years post partum. Socioeconomic status was indicated by maternal education (college graduate vs. less) and family income (>185% vs. ≤185% of the poverty line). Single- and multiple-factor mediation analyses were conducted for socioeconomic disparities in childhood obesity at 6 years, adjusting for demographics.Results: The confounder-adjusted relative risk of childhood obesity was 1.79 for low maternal education and 1.42 for low family income. Low-maternal-education-related obesity was individually mediated by maternal preconception BMI (percentage of indirect effect, 8.8%), smoking during pregnancy (7.0%), infant weight gain (14.4%), child sleep duration (11.4%), and TV viewing during weekdays at 6 years (4.9%). Low-family-income-related obesity was mediated by maternal preconception BMI (18.5%), smoking during pregnancy (6.3%), child sleep duration (12.8%), and the home learning environment at 6 years (26.2%). In multiple-mediator analysis, significant mediators together mediated 54.0% of maternal-education-related or 39.4% of family-income-related disparities.Conclusions: Maternal preconception BMI, smoking during pregnancy, infant weight gain, child sleep, TV viewing, and the home learning environment substantially mediated socioeconomic disparities in childhood obesity in the United States. [ABSTRACT FROM AUTHOR]

Background: Efforts to empower adolescent girls remain constrained by confusion around how to conceptually define empowerment and how to design interventions. More research, particularly among young adolescents, is needed that considers contextual and age-specific circumstances. This paper examines the latent classes of empowerment among early adolescent girls in Bangladesh and factors associated with membership in these classes. Using data from the Bangladeshi Association for Life Skills, Income, and Knowledge for Adolescents project, a four-arm randomized controlled trial designed to evaluate different community-based approaches for adolescents' skills development, we identify the latent classes before and after intervention and explore whether girls' membership in the study arms was associated with latent class membership at endline.Methods: To identify underlying subgroups among the sample, we conducted latent class analysis at baseline and endline using indicators of seven different constructs of empowerment based on the literature. Using multinomial logistic regression analysis, we assessed whether respondents' background characteristics and membership in the study arms were predictive of latent class membership at both timepoints.Results: A three-class model at baseline and a four-class model at endline showed optimal fit. In both models, three distinct latent classes were observed: (1) a least empowered class, (2) a mobile, socially active class, and (3) a socially progressive class. At endline, a fourth class emerged-the most empowered-that was mobile, socially active, and socially progressive. Girls' marital status, religion, and parents' level of education predicted latent class membership; household wealth was predictive at baseline, but not endline. Study arm was also associated with class membership at endline: girls in the Gender-Rights Awareness Arm had the highest probability of belonging to the fourth, most empowered class.Conclusion: This paper identifies and characterizes latent classes of empowerment that exist among the sample before and after the intervention. The apparent differential effects of interventions in predicting latent class membership have implications for community-based programming. Findings suggest that skills-building curriculum focused on promoting gender equitable norms, voice, and agency has potential to influence early adolescent girls across multiple dimensions of empowerment. [ABSTRACT FROM AUTHOR]

This paper investigates the consequences that patients face when their regular general practitioner (GP) closes down her practice, typically due to retirement. We estimate the causal impact of closures on patients' utilization patterns, healthcare expenditures, hospitalizations, mortality, and health plan choices. Employing a difference-in-difference framework, we find that patients who experience a discontinuity of care persistently adjust their ambulatory utilization pattern by shifting visits away from GPs (-12%) toward specialists (+11%) and hospital outpatient facilities (+6%). In contrast, we find no evidence on adverse health effects as measured by hospitalizations and mortality. The impact on utilization is heterogeneous along several dimensions. In particular, we find geographic disparities between regions with high and low availability of primary care. We also observe that patients with chronic conditions substitute more strongly toward other providers. Our results have potential implications for health policy in at least two dimensions: first, practice closures lead to more fragmented care which may entail inefficiencies, and second, closures deteriorate access to primary care in regions with low physician density. [ABSTRACT FROM AUTHOR]

Aim: To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).Method: Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 107 AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 106 hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 107 AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.Results: Infusions (n = 143) were well tolerated, with eight infusion reactions (three in the AlloCB group, five in hCT-MSC) and no other safety concerns. At 12 months, the mean differences (95% confidence intervals [CI]) between actual and expected changes in GMFM-66 score were AlloCB 5.8 points (3.4-8.2), hCT-MSC 4.3 (2.2-6.4), and natural history 3.1 (1.4-5.0). In exploratory, post hoc analysis, the mean GMFM-66 score (95% CI) of the hCT-MSC group was 1.4 points higher than natural history (-1.1 to 4.0; p = 0.27), and the AlloCB group was 3.3 points higher than natural history (0.59-5.93; p = 0.02) after adjustment for baseline Gross Motor Function Classification System level, GMFM-66 score, and etiology.Interpretation: High-dose AlloCB is a potential cell therapy for CP and should be further tested in a randomized, blinded, placebo-controlled trial.What This Paper Adds: Unrelated donor allogeneic umbilical cord blood (AlloCB) and human umbilical cord tissue-derived mesenchymal stromal cell infusion is safe in young children with cerebral palsy. Significant changes in motor function were not observed 6 months after treatment. One year later, treatment with AlloCB was associated with greater increases in Gross Motor Function Measure-66 scores. [ABSTRACT FROM AUTHOR]

Background: Early plasma transfusion is life-saving for bleeding trauma patients. Freeze-dried plasma (FDP) provides unique formulation advantages for infusion in the prehospital setting. We describe characterization and clinical safety data of the first, next-generation FDP stored in plastic bags with rapid reconstitution.Study Design and Methods: Coagulation and chemistry parameters on 155 pairs of fresh frozen plasma (FFP) and their derivative FDP units were compared. Next, a first-in-human, dose-escalation safety evaluation of FDP, involving 24 healthy volunteers who donated either whole blood or apheresis plasma to create autologous FDP, was performed in three dose cohorts (270, 540, and 810 ml) and adverse events (AEs) were monitored. Cohort 3 was randomized, double-blind with a cross-over arm that compared FDP versus FFP using descriptive analysis for AEs, coagulation, hematology, and chemistry parameters.Results: FDP coagulation factors, clotting times, and product quality (pH, total protein, and osmolality) post-lyophilization were preserved. FDP infusions, of up to 810 ml per subject, were found to be safe and with no serious AEs (SAEs) related to FDP. The average time to reconstitute FDP was 67 s (range: 43-106). No differences in coagulation parameters or thrombin activation were detected in subjects infused with 810 ml of FDP compared with FFP.Conclusion: This first next-generation FDP product preserves the potency and safety of FFP in a novel rugged, compressible, plastic container, for rapid transfusion, allowing rapid access to plasma in resuscitation protocols for therapy in acute traumatic hemorrhage. [ABSTRACT FROM AUTHOR]

Is workers' health more sensitive to losses than gains in job security? I address this question using the 1999 rise in the French Delalande tax as a quasi-natural experiment. The tax design allows to separately identify the causal impact of exogenous gains and losses in job security on workers' health. Difference-in-differences estimation results show that a greater job insecurity reduces significantly self-reported health. At the same time, more job security does not translate into a higher level of self-reported health. [ABSTRACT FROM AUTHOR]

Background: Adults with intellectual disabilities often display behaviour that challenges that is a result of biological differences, psychological challenges, and lack of appropriate social support. Intensive Support Teams (IST) are recommended to support the care needs of this group and avoid hospitalisation. However, little attention has been paid to the perspectives of stakeholders who manage, work in, or use ISTs. Method: Interviews and focus groups were conducted with 50 stakeholders (IST service managers and professionals, adults with intellectual disabilities, and family and paid carers) of ISTs. Services operated according to one of two service models previously identified in ISTs in England (enhanced or independent). Results: Thematic analysis identified accessible and flexible support, individualised care, and the involvement of carers and other relevant agencies in management plans and reviews as features of good IST care highlighted by all stakeholder groups. IST managers and professionals described the key challenges of current IST provision as unclear referral criteria, limited interfaces with other local services, and perceived threats associated with funding and staff retention. Findings were similar between the two IST models. Conclusions: ISTs are able to offer care and specialist support that is valued by families, service users and other care providers. However, they face several operational challenges that should be addressed if ISTs are to reach their potential along with community intellectual disability services in supporting adults with intellectual disabilities who display behaviour that challenges in the community. [ABSTRACT FROM AUTHOR]

Objective: This study sought to evaluate the impact of health care strike action on patient mortality.Data Sources: EMBASE, PubMed CINAHL, BIOETHICSLINE, EconLit, WEB OF SCIENCE, and grey literature were searched up to December 2021.Study Design: A systematic review and meta-analysis were utilized.Data Collection/extraction: Random-effects meta-analysis was used to compare mortality rate during strike versus pre- or post-strike, with meta-regression employed to identify factors that might influence the potential impact of strike action. Studies were included if they were observational studies that examined in-hospital/clinic or population mortality during a strike period compared with a control period where there was no strike action.Principal Findings: Seventeen studies examined mortality: 14 examined in-hospital mortality and three examined population mortality. In-hospital studies represented 768,918 admissions and 7191 deaths during strike action and 1,034,437 admissions and 12,676 deaths during control periods. The pooled relative risk (RR) of in-hospital mortality did not significantly differ during strike action versus non-strike periods (RR = 0.91, 95% confidence interval 0.63, 1.31, p = 0.598). Meta-regression also showed that mortality RR was not significantly impacted by country (p = 0.98), profession on strike (p = 0.32 for multiple professions, p = 0.80 for nurses), the duration of the strike (p = 0.26), or whether multiple facilities were on strike (p = 0.55). Only three studies that examined population mortality met the inclusion criteria; therefore, further analysis was not conducted. However, it is noteworthy that none of these studies reported a significant increase in population mortality attributable to strike action.Conclusions: Based on the data available, this review did not find any evidence that strike action has any significant impact on in-hospital patient mortality. [ABSTRACT FROM AUTHOR]

Objective: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.Methods: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m2 , 72.0% female) were enrolled through their PCPs (n = 31). Providers were randomly assigned to refer their patients to a 12-month internet weight-loss intervention only (IWL), the intervention plus semiautomated feedback from the provider (IWL + PCP), or to usual care (EUC). Weight was measured at baseline and at 3, 6, and 12 months.Results: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg in the EUC, IWL, and IWL + PCP groups, respectively. Outcomes were significantly different in EUC versus IWL and EUC versus IWL + PCP (p < 0.001), but not in IWL versus IWL + PCP.Conclusions: Referral by PCPs to an automated weight-loss program holds promise for patients with obesity. Future research should explore ways to further promote accountability and adherence. [ABSTRACT FROM AUTHOR]

Background: STARDOM2 is a randomized, double-blind, phase 3 trial evaluating the efficacy and safety of co-crystal of tramadol-celecoxib (CTC)-a first-in-class analgesic co-crystal comprising racemic tramadol hydrochloride and celecoxib in a supramolecular network that modifies their pharmacokinetic properties-for the management of acute postoperative pain (NCT03062644; EudraCT:2016-000593-38).Methods: Patients with moderate-to-severe pain following abdominal hysterectomy were randomized 2:2:2:2:2:1 to oral CTC 100 mg (rac-tramadol hydrochloride 44 mg/celecoxib 56 mg) twice daily (BID); CTC 150 mg (66/84 mg) BID; CTC 200 mg (88/112 mg) BID; immediate-release tramadol 100 mg four times daily (QID); celecoxib 100 mg BID; or placebo, for 5 days. The primary endpoint was the sum of pain intensity differences over 0-4 h (SPID0-4 ). Key secondary endpoints were rescue medication use within 4 h, 50% response rate at 4 h, and safety/tolerability.Results: Of 1355 patients enrolled, 1138 were randomized (full analysis set) and 1136 treated (safety analysis set). In the prespecified gatekeeping analysis of SPID0-4 , CTC 200 mg was not superior to tramadol but showed non-inferior efficacy (p < 0.001) that was sustained throughout the 120-h period, despite a 5-day cumulative tramadol administration of 880 mg with CTC 200 mg BID versus 2000 mg with tramadol 100 mg QID. Treatment-emergent adverse events (TEAEs) and severe TEAEs were less common with CTC 200 mg versus tramadol. Treatment-related TEAEs were 14.4% with CTC 200 mg and 23.6% with tramadol.Conclusions: Although the study did not meet its primary endpoint, CTC 200 mg showed a clinically relevant improvement in overall benefit/risk profile versus tramadol alone, with considerably lower cumulative opioid exposure.Significance: In the randomized, double-blind, phase 3 STARDOM2 trial-in acute moderate-to-severe pain after abdominal hysterectomy-the novel co-crystal of tramadol-celecoxib (CTC) 200 mg BID was superior to placebo and non-inferior to tramadol 100 mg QID. Although superiority to tramadol was not reached, CTC 200 mg BID exposed patients to lower cumulative opioid (tramadol) doses than tramadol (100 mg QID) alone, with fewer treatment-emergent adverse events. CTC 200 mg thus has a clinically relevant improved benefit/risk profile compared with tramadol alone. [ABSTRACT FROM AUTHOR]

Background: The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain.Methods: Forty healthy participants were enrolled in this double-blinded, randomized, placebo-controlled study. The effect of sumatriptan (n = 20) versus placebo (n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin-induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing.Results: After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome.Conclusions: Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin-induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain.Significance: Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome-specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks. [ABSTRACT FROM AUTHOR]

This three-armed randomized controlled trial examined how moral disengagement and social norms account for change in bullying behavior and their potential as targets of anti-bullying components within separate interventions among 1200 French-speaking Belgian elementary students (48% boys, 9-12 year-olds, 57 classes, nine schools) during 2018-2019 (no ethnicity data available). Mediation analysis revealed that students' moral disengagement successfully decreased (β = -.46), which, in turn, reduced both bullying (β = .33) and outsider behaviors (β = .20), and increased defending (β = -.10). Intervening on social norms decreased bullying (β = -.18), but not through the perceived injunctive class norm as intended. Guidelines to open the "black box" of anti-bullying programs and determine the cost-effectiveness ratio of their components are provided. [ABSTRACT FROM AUTHOR]

Objective: Glucagon-like peptide-1 (GLP-1) receptor agonists recently demonstrated 15% to 20% weight loss in adults with obesity, a range which has previously been achieved only with bariatric surgery. This systematic review and meta-analysis compares weight loss between GLP-1 receptor agonists and bariatric surgery.Methods: The databases MEDLINE, MEDLINE In-Process, MEDLINE Epubs Ahead of Print, Embase Classic + Embase (OvidSP), and Cochrane (Wiley) were searched from inception to April 21, 2021, for randomized controlled trials and observational studies. Two independent reviewers extracted data, reported risk of bias, and graded certainty of evidence. Random-effects models were used to pool change in weight, BMI, and glycated hemoglobin.Results: Six studies, encompassing 332 patients, were included. Among randomized controlled trials, mean difference in weight between all bariatric surgery types and GLP-1 receptor agonists was -22.68 kg (95% CI: -31.41 to -13.96), mean difference in BMI was -8.18 kg/m2 (95% CI: -11.59 to -4.77), and mean difference in glycated hemoglobin was -1.28% (95% CI: -1.94% to -0.61%). Among observational studies, mean difference in weight was -25.11 kg (95% CI: -40.61 to -9.60), and mean difference in BMI was -10.60 kg/m2 (95% CI: -17.22 to -3.98). Only one observational study reported glycemic outcomes.Conclusion: In adults with obesity, bariatric surgery still confers the highest reductions in weight and BMI but confers similar effects in glycemic control when compared with GLP-1 receptor agonists. [ABSTRACT FROM AUTHOR]

Before embarking on an individual participant data meta-analysis (IPDMA) project, researchers and funders need assurance it is worth their time and cost. This should include consideration of how many studies are promising their IPD and, given the characteristics of these studies, the power of an IPDMA including them. Here, we show how to estimate the power of a planned IPDMA of randomized trials to examine treatment-covariate interactions at the participant level (ie, treatment effect modifiers). We focus on a binary outcome with binary or continuous covariates, and propose a three-step approach, which assumes the true interaction size is common to all trials. In step one, the user must specify a minimally important interaction size and, for each trial separately (eg, as obtained from trial publications), the following aggregate data: the number of participants and events in control and treatment groups, the mean and SD for each continuous covariate, and the proportion of participants in each category for each binary covariate. This allows the variance of the interaction estimate to be calculated for each trial, using an analytic solution for Fisher's information matrix from a logistic regression model. Step 2 calculates the variance of the summary interaction estimate from the planned IPDMA (equal to the inverse of the sum of the inverse trial variances from step 1), and step 3 calculates the corresponding power based on a two-sided Wald test. Stata and R code are provided, and two examples given for illustration. Extension to allow for between-study heterogeneity is also considered. [ABSTRACT FROM AUTHOR]

Aim: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations.Methods: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups.Results: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed.Conclusion: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits. [ABSTRACT FROM AUTHOR]

Objective: Soft tissue sarcomas (STS) and gastrointestinal stromal tumours (GIST) are a group of rare malignant tumours with a high and heterogenous disease burden. As evidence is scarce, we analysed the prevalence of increased emotional distress and identified distress-associated factors in these patients.Methods: The PROSa-study (Burden and medical care of sarcoma) was conducted between 2017 and 2020 in 39 study centres. Cross-sectional data from adult STS and GIST patients were analysed. Distress was measured with the Patient Health Questionnaire (PHQ-4). The relation of socioeconomic and clinical factors with distress was explored in adjusted logistic regression models.Results: Among 897 patients, 17% reported elevated anxiety and 19% reported depression. Unemployed patients (odds ratio [OR] 6.6; 95% CI 2.9-15.0), and those with a disability pension (OR 3.1; 95% CI 1.9-5.0) were more likely to experience distress compared to employed patients. Also, patients with a disability pass had higher odds of increased distress than those without (OR 1.8; 95% CI 1.2-2.7). Lowest distress was observed in patients 2 to <5 years and ≥5 years after diagnosis (comparison: <6 months) (OR 0.4; 95% CI 0.2-0.6) and (0.3; 95% CI 0.2-0.6). Patients with thoracic STS (vs. lower limbs) had twice the odds to experience distress (OR 2.0; 95% CI 1.1-3.6). Distress was seen almost twice as often in patients with progressive disease (vs. complete remission) (OR 1.7; 95% CI 1.1-2.8).Conclusion: The prevalence of elevated distress in STS and GIST patients is high. In unemployed patients, in those with a disability pension and in newly diagnosed patients a noticeable increase was observed. Clinicians should be aware of these factors and consider the social aspects of the disease. [ABSTRACT FROM AUTHOR]

Background: Tissue regeneration within the periodontally involved furcation area is one of the most challenging aspects of periodontal surgery. The aim of this study was to evaluate the additional benefit of leukocyte and platelet-rich fibrin (L-PRF) to autogenous bone grafts (ABGs) in the treatment of mandibular molar degree II furcation involvement, comparing the clinical outcomes with those from open flap debridement (OFD)+ABG and OFD alone treatments.Methods: Fifty-four patients, exhibiting one buccal or lingual mandibular molar furcation defect, were randomly assigned to three treatment groups: OFD+ABG+L-PRF (n = 18); OFD+ABG (n = 18); and OFD (n = 18). Clinical (probing depth [PD], horizontal clinical attachment level [HCAL], vertical clinical attachment level [VCAL], gingival recession [GR]) and radiographic (vertical bone level [VBL]) parameters were evaluated at baseline and 6 months after treatment. HCAL change was the primary outcome.Results: No significant differences within each group were reported for GR changes, but statistically significant improvements in HCAL, VCAL, PD, and VBL were observed in all groups, except for VBL in the OFD group. At 6 months, the mean HCAL gain was 2.29 ± 0.18 mm in the OFD+ABG+L-PRF group, which was significantly greater than that in the OFD+ABG (1.61 ± 0.18 mm) and OFD (0.86 ± 0.18 mm) groups. Both OFD+ABG+L-PRF and OFD+ABG therapies produced a significantly greater clinical and radiographic improvement than OFD.Conclusion: The addition of L-PRF to ABG produces a significantly greater HCAL gain and PD reduction as compared with OFD+ABG treatment in mandibular degree II furcation involvements. [ABSTRACT FROM AUTHOR]

A collection of clinical trials presumed to be measuring the same effect provides two ways of estimating the variance of the overall estimate of an effect, or equivalently its precision. Furthermore, the true precision of the treatment effect from trial to trial is identical and the number of degrees of freedom available within each trial are also identical. The first is that of inherent treatment heterogeneity: the treatments may differ in their nature from trial to trial, not because different populations react differently to the same treatment but because what is being regarded as one treatment by the meta-analyst is present in two or more versions. Table 1 shows the number of degrees of freedom involved for each trial and also the corresponding meta-analytic inflation factor that would apply were it the case that all other trials were the size of the trial in question. [Extracted from the article]

Research on the timing of events during the transition to adulthood, such as first union, sex, and birth in low- and middle-income countries (LMICs), focused predominantly on measures of central tendency, notably median or mean ages. In this report, we adopt a different perspective on this topic by examining disparities in the timing of these events in 46 LMICs spanning four decades. Using Demographic and Health Surveys, we estimate ages at which 25 percent, 50 percent, and 75 percent of women have first union, birth, and sex. We compute interquartile ranges to measure within-country variation and disparities in the timing of sexual initiation and family formation. Variation in the timing of first union, birth, and sex generally increases as the median ages at these events increase. Disparities in the timing of first union and birth grew in West Africa and Latin America, and women who experience these events relatively early increasingly lag behind women who experience them relatively late. Documenting trends in measures of central tendency is insufficient to capture the complexity of ongoing changes because they mask growing disparities in the timing of family formation across many LMICs. These results are important for assessing progress toward the achievement of sustainable development goals related to the reduction of early marriages and pregnancies and highlight a need for more holistic approaches to measure the timing of family formation. [ABSTRACT FROM AUTHOR]

Human laboratory studies are widely used to evaluate behavioural mechanisms of pharmacotherapy effects. Results from human laboratory studies examining smoking cessation pharmacotherapies have not been examined in aggregate. The current meta-analysis aimed to synthesize data from randomized, placebo-controlled human laboratory studies on the effects of non-nicotine pharmacotherapies on outcomes relevant for smoking cessation. Literature searches identified 15 human laboratory studies of varenicline (n = 697) and 9 studies of bupropion (n = 313) with sufficient data for inclusion. Studies involved acute or subacute pharmacotherapy treatment with administration durations ranging from a single dose to 8 weeks. Primary outcomes examined were craving, withdrawal and behavioural indices of smoking. Varenicline significantly reduced craving (Hedge's g = -0.36[-0.54,-0.17], p < 0.001), withdrawal (g = -0.25[-0.41,-0.09], p = 0.003) and behavioural indices of smoking (g = -0.36[-0.63,-0.08], p = 0.01) relative to placebo. In contrast, results were inconclusive regarding bupropion's effects on craving (g = -0.13[-0.32,0.05], p = 0.15), withdrawal (g = -0.15[-0.44,0.14], p = 0.31) and behavioural indices of smoking (g = -0.05[-0.35,0.24], p = 0.73) relative to placebo. Findings provide meta-analytic support that short-term varenicline treatment decreases craving, withdrawal symptoms and smoking behaviour under controlled laboratory conditions. However, findings also suggest the ability of human laboratory paradigms to detect pharmacotherapy effects may differ by treatment type. Pharmacotherapy discovery and evaluation efforts utilizing human laboratory methods should aim to align study designs and laboratory procedures with presumed therapeutic mechanisms when possible. [ABSTRACT FROM AUTHOR]

Objective: The postpartum period is a key life stage, contributing to increased maternal obesity risk. Current lifestyle interventions do not consider the role of a woman's partner in reducing stress and supporting lifestyle change. The objective of this study was to assess the effect of an intervention that seeks to enhance coparenting relationship quality on maternal BMI from before conception to 12 months post partum and whether the intervention moderated the association of changes in cortisol and BMI.Methods: A randomized controlled trial was used to assess an intervention (eight classes: four during and four following pregnancy) focusing on enhancing couple coparenting relationships during pregnancy and post partum (n = 57) compared with standard care (n = 53).Results: The main outcome measures were changes in maternal BMI and cortisol. There was a smaller increase in BMI for mothers in intervention compared with control groups (mean [SE], -1.03 [0.42] kg/m2 , p = 0.015). There was an interaction between intervention status and cortisol change predicting BMI change (p = 0.026), such that cortisol change significantly predicted BMI change among mothers in the control (p = 0.049) but not the intervention groups (p = 0.204).Conclusions: A coparenting intervention improved maternal postpartum BMI, with this effect potentially related to ameliorating the negative effect of stress, as measured by cortisol, on BMI. The role of enhanced coparenting in improving maternal anthropometry warrants urgent attention. [ABSTRACT FROM AUTHOR]

Background: To date, the efficacy of ridge preservation in the maintenance of the residual alveolar ridge dimension beyond 6 months after treatment is unknown. The purpose of this study was to compare the differences in alveolar ridge dimensional change following ridge preservation between 4- and 12-month healing time points using cone-beam computed tomography (CBCT).Methods: Fifty seven patients planned for tooth extraction and implant placement were enrolled. Following extraction, ridge preservation was performed. CBCT scans were taken within 72 hours following extraction with a customized resin stent containing a fixed radiographic marker. At either 4 months (short-term, ST group) or 12 months (long-term, LT group) after ridge preservation, patients had a second CBCT taken and an implant placed. Changes in ridge height and width were measured using the standardized radiographic marker.Results: No significant differences were detected between the ST and LT groups in loss of buccal and lingual ridge height. Similarly, when adjusted for baseline ridge width, no significant differences were detected in ridge width loss at 3, 5, and 7 mm apical to the crest between the ST and LT groups.Conclusions: The efficacy of ridge preservation in the maintenance of ridge width and height at the 12-month time point is similar to that of the 4-month time point. Clinicians may feel confident that a delay in implant placement for up to a year has no significant negative impact on the height and width of the healed ridge. [ABSTRACT FROM AUTHOR]

Background: Along with the popularity of dental implants, implant esthetic complications are also on the rise. Recently a classification was proposed to comprehensively evaluate these conditions, with the definition of peri-implant soft tissue dehiscence/deficiencies (PSTDs). The aim of this article was therefore to test the inter-examiner agreement when utilizing the established rubrics among 25 standardized cases and 34 clinicians of different skill levels.Methods: Twelve periodontal residents, 12 general dentists, and 10 periodontists participated in this study. All examiners were provided with photographs of 25 single PSTDs and asked to rate all cases based on the proposed classification at a single timepoint. Variance components analysis was conducted with multilevel regression fit in a Bayesian framework to obtain uncertainty intervals for fractional variance contributions and interclass correlation values (ICC) to assess the agreement in the rating of all cases, among all examiners, different skill-level practitioners, and to compare their responses relative to the judgment of a gold standard examiner.Results: Overall, the results showed reproducible and consistent responses among the 34 examiners, and in each subgroup of skill-level, comparable to that of the gold examiner. Nevertheless, periodontists and residents were more likely to agree with the response of the gold standard examiner in their assessments of class and subclass of the PSTDs.Conclusions: The proposed PSTD classification showed reproducible assessments among all examiners, and between examiners of the same skill-level. The response of the gold standard examiner was more in line with the assessment of the periodontists and periodontal residents. [ABSTRACT FROM AUTHOR]

Objectives: Accumulating evidence suggests that hearing loss (HL) treatment may benefit depressive symptoms among older adults with Major Depressive Disorder (MDD), but the specific individual characteristics of those who stand to improve most are unknown.Methods: N = 37 patients ≥60 years with HL and MDD received either active or sham hearing aids in this 12-week double-blind randomized controlled trial. A combined moderator approach was utilized in the analysis in order to examine multiple different pretreatment individual characteristics to determine the specific qualities that predicted the best depressive symptom response to hearing aids. Pretreatment characteristics included: Hearing Handicap Inventory for the Elderly (HHIE-S), pure tone average (PTA), speech reception threshold (SRT), Short Physical Performance Battery (SPPB), cognition (Repeatable Battery for the Assessment of Neuropsychological Status).Results: The analysis revealed a combined moderator, predicting greater improvement with active versus sham hearing aids, that had a larger effect size than any individual moderator (combined effect size [ES] = 0.49 [95% CI: 0.36, 0.76]). Individuals with worse hearing-related disability (HHIE-S: individual ES = -0.16), speech recognition (SRT: individual ES = -0.14), physical performance (SPPB: individual ES = 0.41), and language functioning (individual ES = 0.19) but with relatively less severe audiometric thresholds (PTA: individual ES = 0.17) experienced greater depressive symptom improvement with active hearing aids.Conclusions: Older adults with relatively worse HL-related, physical, and cognitive functioning may stand to benefit most from hearing aids. Given the large number of older adults experiencing HL and MDD, a non-invasive and scalable means of targeting those most likely to respond to interventions would be valuable. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of cervical pessary, as a strategy to prevent preterm birth (PTB), on the outcome of subsequent pregnancy and maternal quality of life 4 years after the index twin pregnancy.Methods: Between 2009 and 2012, the ProTWIN trial randomized women with a multiple pregnancy to pessary use vs standard care for the prevention of PTB. The trial showed no benefit in unselected women with a twin pregnancy, but showed a 60% reduction in poor perinatal outcomes in favor of the pessary group in the subgroup of women with a mid-trimester short cervix (cervical length < 38 mm). All women were invited to participate in a follow-up study 4 years after their participation in the ProTWIN trial. In this follow-up study, maternal quality of life was assessed using the EQ-5D-3L questionnaire and women were asked separate questions about subsequent pregnancies. Results were compared between women who were randomized to the pessary vs the control group in the ProTWIN trial by calculating relative risk (RR) and 95% CI. Subgroup analysis was performed for women with a mid-trimester short cervix (cervical length < 38 mm).Results: Of the 813 women included in the ProTWIN trial, 408 (50.2%) participated in this follow-up study, comprising 228 randomized to the pessary group and 180 to the control group in the original trial. The median interval between participation in the ProTWIN trial and participation in this follow-up study was 4.1 (interquartile range (IQR), 3.9-7.1) years. Ninety-eight (24.0%) participants tried to conceive after their participation in the ProTWIN trial. Of those, 22 (22.4%) women did not have a subsequent pregnancy (no difference between pessary and control groups), seven (7.1%) women had at least one miscarriage but no live birth, and 67 (68.4%) women had at least one live birth (35 in the pessary vs 32 in the control group; RR, 0.93 (95% CI, 0.8-1.07)). In two women, the pregnancy outcome was unknown. Preterm delivery (< 37 weeks of gestation) of the first live birth occurred in three women in the pessary vs one woman in the control group (all singleton; RR, 2.57 (95% CI, 0.28-23.44)). No differences were found between the pessary and control groups in the subgroup of women with mid-trimester short cervix, but the numbers analyzed were small. The median health state index score was 0.95 (IQR, 0.82-0.95), with no difference between the pessary and control groups.Conclusion: Our findings suggest that there are no long-term effects of pessary use on the outcome of subsequent pregnancies and maternal quality of life. Data on obstetric outcome were limited due to the small numbers. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188).Methods: This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks.Results: Sixty-three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, -2.29; Cohen d, -0.32). The mean between-group difference scores in caregiver quality of life was -1.56 (usual care - intervention; d, -0.07). Similar outcome results were observed for patient participants.Conclusions: The authors piloted ENABLE Cornerstone, an intervention for African American and rural-dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising.Lay Summary: To date, very few programs have been developed to support under-resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented. [ABSTRACT FROM AUTHOR]

Objective: Delirium is a common postoperative complication of hip fracture. Various methods exist to detect delirium as a reference standard. The goal of this study was to characterize the properties of the measures obtained in a randomized controlled trial, to document their relationship to the Diagnostic and Statistical Manual of Mental Disorders:Text Revision based diagnosis of postoperative delirium by a consensus panel, and to describe the method in detail to allow replication by others.Methods: A secondary analysis of the randomized trial STRIDE (A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients) was conducted. Delirium assessments were performed in 200 consecutive hip fracture repair patients ≥65 years old. Assessors underwent extensive training in delirium assessment and the final delirium diagnosis was adjudicated by a consensus panel of three physicians with expertise in delirium assessment.Results: A total of 680 consensus panel delirium diagnoses were completed. There were only 19 (2.8%, 19/678) evaluations where the delirium adjudication by the consensus panel differed from delirium findings by the Confusion Assessment Method (CAM). In 16 (84%, 16/19) of the cases, CAM was negative but the consensus panel diagnosed the patient as having delirium based on all of the available information including the CAM.Conclusion: The consensus panel diagnosis was more sensitive compared to CAM alone, however the magnitude of the difference was not large. When assessors are well trained and delirium assessments are closely supervised throughout the study, CAM may be adequate for delirium diagnosis in a clinical trial. Future studies are needed to test this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Global initiatives that promote public health responses to dementia have resulted in numerous countries developing new national policies. Current policy guidelines in England, for example, recommend that people diagnosed with mild-to-moderate dementia receive information and psychosocial interventions to improve their ability to 'live well'. However, it remains unclear to what extent these recommendations are being achieved.Methods: Self-reported information from 1537 people living with dementia and informant-reported information from 1277 carers of people living with dementia was used to quantify receipt of community-based dementia support services, including health and social care services provided by statutory or voluntary-sector organisations, in Britain from 2014 to 2016. Demographic factors associated with differences in receipt of support services were also investigated to identify particularly vulnerable groups of people living with dementia.Results: Both self- and informant reports suggested that approximately 50% of people living with dementia received support services for dementia. Receipt of support services was lower among people living with dementia who are older, female, and have fewer educational qualifications. Receipt of support services also differed according to diagnosis and carer status, but was unrelated to marital status.Conclusions: Limited receipt of dementia support services among people living with dementia in Britain provides a baseline to assess the efficacy of current policy guidelines regarding provision of information and support. Targeted efforts to facilitate receipt of support services among the particularly vulnerable groups identified in the current study could improve the efficacy of dementia support services both in Britain and internationally, and should inform policy development. [ABSTRACT FROM AUTHOR]

Background and Purpose: Ilexgenin A is a triterpenoid from ShanLv Cha with beneficial effects on metabolic homeostasis. We investigated whether ilexgenin A could inhibit hepatic de novo fatty acid synthesis via the interfering with SREBP1 maturation.Experimental Approach: The effects of Ilexgenin A on CRTC2 translocation and SREBP1 maturation were investigated in the liver of fasted mice and hepatocytes exposed to saturated fatty acids. The effect of Iilexgenin A on hepatic lipid accumulation was also observed in high-fat diet fed mice.Key Results: Sec23A and Sec31A are two subunits of COPII complex and their interaction is essential for the processing of SREBP1 maturation. Ilexgenin A activates AMPK by reducing cellular energy and preventing cytoplasmic CRTC2 to compete with Sec23A for binding to Sec31A under nutrient-rich conditions. Consequently, ilexgenin A impaired COPII-dependent SREBP1 maturation via disrupting Sec31A-Sec23A interaction, leading to the inhibition of de novo fatty acid synthesis in the liver. In contrast, mTORC1 phosphorylated Ser136 of CRTC2, facilitating the formation of Sec31A-Sec23A interaction to promote SREBP1 maturation, whereas this action was reversed by ilexgenin A in an AMPK-dependent manner. Ilexgenin A protected CRTC2 function and restrained hepatic lipogenic response in high fat diet-fed mice, providing in vivo evidence to support the beneficial effects of ilexgenin A on lipid metabolism.Conclusions and Implications: Ilexgenin A activated AMPK and restrained CRTC2 to the cytoplasm to prevent SREBP1 maturation via impairing COPII function in the liver. This suggests that CRTC2 might be a potential target for pharmacological intervention to prevent hepatic lipid deposition.Linked Articles: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc. [ABSTRACT FROM AUTHOR]

Reduced inhibitory control and a hypersensitivity to reward are key deficits in drug dependents; however, they tend to be studied in isolation. Here, we seek to understand the neural processes underlying control over reward and how this is different in people with a tobacco use disorder (pTUD). A novel variant of the monetary incentive delay task was performed by pTUD (n = 20) and non-smokers (n = 20), where we added a stop-signal component such that participants had to inhibit prepotent responses to earn a larger monetary reward. Brain activity was recorded using functional magnetic resonance imaging (fMRI). We estimated stop signal reaction times (SSRTs), an indicator of impulsivity, and correlated these with brain activity. Inhibitory accuracy scores did not differ between the control group and pTUD. However, pTUD had slower SSRTs, suggesting that they may find it harder to inhibit responses. Brain data revealed that pTUD had greater preparatory control activity in the middle frontal gyrus and inferior frontal gyrus prior to successful inhibitions over reward. In contrast, non-smokers had greater reactive control associated with more activity in the anterior cingulate cortex during these successful inhibitions. SSRT-brain activity correlations revealed that pTUD engaged more control-related prefrontal brain regions when SSRTs are slower. Overall, while the inhibition accuracy scores were similar between groups, differential neural processes and strategies were used to successfully inhibit a prepotent response. The findings suggest that increasing preparatory control in pTUD may be one possible treatment target in order to increase inhibitory control over reward. [ABSTRACT FROM AUTHOR]

Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery. [ABSTRACT FROM AUTHOR]

As the opioid crisis has continued to grow, so has the number of infants exposed to opioids during the prenatal period. A growing concern is that prenatal exposure to opioids may induce persistent neurological changes that increase the propensity for future addictions. Although alcohol represents the most likely addictive substance that the growing population of prenatal opioid exposed will encounter as they mature, no studies to date have examined the effect of prenatal opioid exposure on future sensitivity to alcohol reward. Using a recently developed mouse model of prenatal methadone exposure (PME), we investigated the rewarding properties of alcohol and alcohol consumption in male and female adolescent PME and prenatal saline exposed (PSE) control animals. Conditioned place preference to alcohol was disrupted in PME offspring in a sex-dependent manner with PME males exhibiting resistance to the rewarding properties of alcohol. Repeated injections of alcohol revealed enhanced sensitivity to the locomotor-stimulating effects of alcohol specific to PME females. PME males consumed significantly more alcohol over 4 weeks of alcohol access relative to PSE males and exhibited increased resistance to quinine-adulterated alcohol. Further, a novel machine learning model was developed to employ measured differences in alcohol consumption and drinking microstructure to reliably predict prenatal exposure. These findings indicate that PME alters the sensitivity to alcohol reward in adolescent mice in a sex-specific manner and suggests prenatal opioid exposure may induce persistent effects on reward neurocircuitry that can reprogram offspring behavioural response to alcohol later in life. [ABSTRACT FROM AUTHOR]

Previous studies have established a role of sex hormones in alcohol use disorder (AUD).Only few clinical investigations with low numbers of patients with AUD have focused on the sulphated form of dehydroepiandrosterone (DHEA-S), despite its function as a neuromodulating sex steroid on receptors in the central nervous system (γ-aminobutyric acid type A, N-methyl-D-aspartate, sigma-1 receptors). DHEA-S serum levels were compared between 200 inpatients with AUD (44% women) admitted for withdrawal treatment and 240 healthy controls (45% women) and analysed longitudinally in patients from early abstinence (baseline) to a median of 5 days later. We also correlated DHEA-S levels with craving, liver enzyme activities, and prospective alcohol-related readmissions during a 24-month follow-up. DHEA-S concentrations were lower in female patients than in female healthy controls during baseline (70%) and decreased from baseline to follow-up in the female and male patients groups (down to: women, 92%; men, 76%). Baseline DHEA-S concentrations correlated with the total and obsessive subscales of the Obsessive-Compulsive Drinking Scale and with maximum visual analogue scale craving scores in female patients (Rho ≤ -0.240) and gamma-glutamyl transferase activity in female (Rho = -0.292) and male (Rho = -0.391) patients. DHEA-S did not significantly predict outcome. We found interactions with smoking behaviour and age. This is the first study based on large cohorts of inpatients with AUD undergoing a qualified detoxification treatment to provide sex-separated evidence for associations of DHEA-S serum concentrations with AUD and related phenotypes. The results stimulate further investigations whether DHEA-S directly influences alcohol craving building a basis to develop sex-sensitive prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse. Behavioural and functional magnetic resonance imaging (fMRI) data from a modified monetary incentive delay task were compared between participants with and without FH (FH positive [FH+]: n = 76 and FH negative [FH-]: n = 69; 76 with ADHD, aged 16.74 ± 3.14, 82 males), while accounting for continuous ADHD scores. The main analysis showed distinct positive association between ADHD scores and reaction times during neutral versus reward condition. ADHD scores were also positively associated with anticipatory responses of dorsolateral prefrontal cortex, independent of FH. There were no main FH effects on brain activation. Yet, FH+ participants showed distinct neural alterations in ventrolateral prefrontal cortex (VLPFC), dependent on ADHD. This was driven by positive association between ADHD scores and VLPFC activation during reward outcome, only in FH+. Sensitivity analysis with stricter SUD index showed hyperactivation of anterior cingulate cortex for FH+, independent of ADHD, during reward anticipation. There were no FH or ADHD effects on activation of ventral striatum in any analysis. Findings suggest both FH and ADHD effects in circuits of reward and attention/memory during reward processing. Future studies should examine whether these relate to early substance use initiation in ADHD and explore the need for adjusted SUD prevention strategies. [ABSTRACT FROM AUTHOR]

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph  = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA  = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (βself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (βco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to research the role and underlying mechanism of miR-195 involved in pancreatic β-cell dedifferentiation induced by hyperlipemia in type 2 diabetes mellitus.Methods: High-fat-diet-induced obese C57BL/6J mice and palmitate-stimulated Min6 cells were used as the models of β-cell dedifferentiation in vivo and in vitro, respectively. The expression of miR-195 and insulin secretion during β-cell dedifferentiation were measured. Also, the influence of regulated miR-195 expression on β-cell dedifferentiation was examined. Meanwhile, the IRS-1/2/Pi3k/Akt pathway and mitofusin-2 (Mfn2) expression were investigated during β-cell dedifferentiation.Results: MiR-195 was upregulated during lipotoxicity-induced β-cell dedifferentiation in both in vivo and in vitro experiments, and miR-195 functionally contributed to lipotoxicity-induced β-cell dedifferentiation. Furthermore, miR-195 inhibited IRS-1/2/Pi3k/Akt pathway activation, which accompanied β-cell dedifferentiation. Mfn2, a target of miR-195, was found to be downregulated and was associated with increased mitochondrial production of reactive oxygen species during β-cell dedifferentiation. Instructively, inhibition of miR-195, at least partially, reversed the downregulation of Mfn2, restored IRS-1/2/Pi3k/Akt pathway activation, and prevented β-cell dedifferentiation.Conclusions: MiR-195 promoted β-cell dedifferentiation through negatively regulating Mfn2 expression and inhibiting the IRS-1/2/Pi3k/Akt pathway, providing a promising treatment for type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess gut microbiota modifications after exercise in humans and animal models with obesity or type 2 diabetes and their role in exercise-induced weight loss.Methods: A systematic search of six databases was conducted on July 31, 2021. The extracted data on body fat or body weight from human and animal studies were analyzed using random-effects meta-analysis.Results: A total of 28 studies were included, with all studies reporting exercise-induced gut microbiota modifications; however, the modified taxa varied among studies. Proteobacteria was the only taxa reported to be altered by exercise in more than one human and one animal study. Taxa belonging to Firmicutes were the most responsive to exercise in humans and mice, whereas Proteobacteria taxa were the most responsive to exercise in rats. A meta-analysis was conducted to examine the weight-lowering effect of exercise based on data subgrouped by altered or unaltered α-diversity or β-diversity. The association between the weight-lowering effect of exercise and altered β-diversity was observed in humans with obesity but not in animals.Conclusions: These findings suggest that gut microbiota modifications contribute to exercise-induced weight loss in obesity; however, their precise contributions, especially those of taxon-level variations, remain to be investigated. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to examine the effects of tryptophan consumption on obesity and type 2 diabetes (T2D) risk and whether sleep duration mediates these effects.Methods: Overall, data of 7,908 participants were obtained from the China Health and Nutrition Survey (1997-2011). A total of 6,373 and 4,398 participants who reported sleep duration and had blood samples, respectively, were incorporated into subgroup analyses. Multivariate Cox regression models were used to assess the associations between tertiles of tryptophan intake with obesity and T2D. General linear regression models were used to evaluate the effect of tryptophan on sleep time and plasma biomarkers.Results: Dietary tryptophan was significantly associated with decreased risk of obesity and T2D risk (hazard ratio tertile 3 to tertile 1 : 0.602 [95% CI: 0.500-0.724]; 0.693 [95% CI: 0.565-0.850]). Sleep duration was significantly higher, and hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-100 (APO-B) were lower in the high tertile of tryptophan compared with the low tertile (p < 0.05). In addition, mediation effects on the associations of tryptophan intake with obesity and T2D risk were observed for sleep duration (estimated mediation percentage: 31.902% and 37.391%).Conclusions: Dietary tryptophan showed advantageous effects on obesity and T2D risk. Furthermore, sleep duration potentially mediated for these effects. [ABSTRACT FROM AUTHOR]

Objective: A first-in-human responsive deep brain stimulation (rDBS) trial (NCT03868670) for obesity is under way, which is based on promising preclinical evidence. Given the upfront costs of rDBS, it is prudent to examine the success threshold for cost-effectiveness compared with laparoscopic Roux-en-Y gastric bypass (LRYGB).Methods: Efficacy and safety data on LRYGB and safety data on rDBS were collected for established indications through a literature search. The success threshold was defined as minimum BMI reduction. Treatment costs were calculated via Medicare national reimbursement data.Results: LRYGB had a mean BMI reduction of 13.75 kg/m2 . Based on adverse events, LRYGB was a less-preferred health state (overall adverse event utility of 0.96 [0.02]) than rDBS (0.98 [0.01]), but LRYGB ($14,366 [$6,410]) had a significantly lower treatment cost than rDBS ($29,951 [$4,490]; p < 0.0001). Therefore, for rDBS to be cost-effective compared with LRYGB, the multiple models yielded a success threshold range of 13.7 to 15.2 kg/m2 .Conclusions: This study established a preliminary efficacy success threshold for rDBS to be cost-effective for severe obesity, and results from randomized controlled trials are needed. This analysis allows for interpretation of the economic impact of advancing rDBS for obesity in light of ongoing trial results and suggests an attainable threshold is needed for cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objective: This review examines main government and nongovernmental institutions for childhood obesity prevention and control in China, as well as major national interventions for childhood obesity.Methods: PubMed, China National Knowledge Infrastructure (CNKI), Wanfang, official websites of national governments and professional institutions/associations, Baidu.com, and Google.com were systematically searched in March 2020 to April 2020. A total of 20 international and national experts on childhood obesity were surveyed.Results: "Government-led multisector cooperation" obesity-related intervention systems have been formed. National-level interventions were mainly implemented by the Chinese State Council and its administrative departments, along with national professional institutions/associations. Provincial, municipal, and county governments and their subordinate departments coordinated local works. Actions taken by these sectors to fight childhood obesity included developing and implementing regulations and laws, health standards and practice guidelines, surveillance for obesity and related determinants, governmental budget and research funds, and interventions. A total of 14 major national childhood obesity-related interventions were found: comprehensive interventions (e.g., "Healthy Lifestyle for All campaign," 2007), diet and nutrition (e.g., "Chinese Rural Compulsory Education Student Nutrition Improvement Program," since 2011), and physical activity (e.g., "Happy 10 Minutes Program," 2006).Conclusions: Although obesity-related intervention systems and national interventions were implemented, more efforts and stronger government leadership and commitment are needed. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the effects of infrared light laser therapy (ILLT) on ligature-induced periodontitis in rats using micro-computed tomography (micro-CT), histology, fibroblast migration, and viability analysis.Methods: Forty-eight rats were randomly distributed into three groups: control (no periodontitis), PDC (periodontitis without laser therapy), and PD+L (periodontitis with laser therapy). Periodontitis was induced by ligature placement for 4 weeks. The 12-week-old rats (baseline) were subjected to laser treatment and euthanized 30 days after. After treatment, the mandibular first molars were prepared for micro-CT scanning, and histological sections were assessed as to the cementoenamel junction, alveolar bone crest, and polymorphonuclear (PMN) cell infiltration. In vitro assays were carried out to examine NIH/3T3 fibroblast viability after laser therapy.Results: Migration and cell viability assays revealed that the ILLT maintained fibroblast cell viability with 4 J/cm2 , reaching 100% healing. The control group (at baseline and 30 days) presented a statistically significant difference from the PDC group at 30 days in terms of distance from the cementoenamel junction to the alveolar bone crest (CEJ-ABC). The PD+L group showed a statistically substantial difference from the PDC group at 30 days in terms of trabecular thickness (Tb.Th), degree of anisotropy (DA), and closed porosity percentage (Po%).Conclusion: ILLT seemed to preserve the bone structure in the in vivo periodontitis induction model at 30 days and did not reduce cell viability or increase fibroblast migration in vitro. The ILLT provides positive effects on mandibular bone microstructure. [ABSTRACT FROM AUTHOR]

Background: The aim of this clinical trial was to evaluate the effect of a periodontal health education session (PHES), which included education on the pathogenesis and consequences of periodontal diseases on oral hygiene motivation in patients with gingivitis.Methods: A randomized controlled clinical trial was conducted on 50 (26 females and 24 males) patients with gingivitis who underwent periodontal treatment. Subjects were randomly allocated into the PHES group (experimental group) and standard oral hygiene education group (control group). The Rustogi Modified Navy Plaque Index (RMNPI) and Papillary Bleeding Index (PBI) were used to evaluate oral hygiene at baseline and were repeated after 1, 3, and 6 months. Knowledge about periodontal disease was measured and the participants' motivation was determined using the Oral Hygiene Motivation Scale.Results: Although baseline knowledge levels and motivation scores were not different between the groups, following the educational motivational interviewing (MI) session, levels were higher in the experimental compared with the control group. The subjects' RMNPI and PBI scores at the 1-, 3-, and 6- month re-examinations were statistically higher in the control group than the experimental group. Furthermore, the level of knowledge and intrinsic and total motivation scores were moderately positively correlated with a reduction in clinical indices at 6 months compared with baseline.Conclusions: The results of this study indicated that increased knowledge and awareness about periodontal diseases and its consequences, including systemic effects, via educational MI session increased intrinsic motivation and improved oral hygiene of patients with gingivitis, especially regarding interproximal surfaces. [ABSTRACT FROM AUTHOR]

Background: This randomized, crossover trial sought to determine if a preoperative intravenous (IV) dose of dexamethasone reduces pain, swelling, and analgesic usage following periodontal surgery.Methods: Thirty-seven patients planned for two similar periodontal flap surgeries under IV sedation were enrolled. Patients were randomized to receive either 2 mL (8 mg) dexamethasone sodium phosphate or 2 mL of IV solution (placebo) before the first surgery, and 2 mL of the other solution before the second surgery. Postoperative discomfort was managed with a standardized regimen of 600 mg ibuprofen and 325 mg acetaminophen. A smartphone application was used to record self-assessed pain and swelling scores using 21-point numerical (NRS-21) and 4-point verbal (VRS-4) rating scales as well as the number of analgesic medications taken at 12-, 24-, 48-, 72-, 168-, and 336-hours following each surgery.Results: IV dexamethasone was associated with a significant reduction in pain at 12, 24, 48, and 72 hours (P <0.05), and swelling at 12, 24, 48, and 168 hours (P < 0.05) postoperatively when compared with placebo based on NRS-21 responses. VRS-4 data showed significant reductions in pain at 12, 72, and 168 hours and swelling at 12, 24, and 168 hours postoperatively with dexamethasone. No significant differences were found in the number of tablets of ibuprofen or acetaminophen between dexamethasone and placebo surgeries.Conclusions: Preoperative, intravenously administered dexamethasone reduces pain and swelling within the first postoperative week following periodontal flap surgery and should be considered a useful adjunct for perioperative management. [ABSTRACT FROM AUTHOR]

The main purpose of many medical studies is to estimate the effects of a treatment or exposure on an outcome. However, it is not always possible to randomize the study participants to a particular treatment, therefore observational study designs may be used. There are major challenges with observational studies; one of which is confounding. Controlling for confounding is commonly performed by direct adjustment of measured confounders; although, sometimes this approach is suboptimal due to modeling assumptions and misspecification. Recent advances in the field of causal inference have dealt with confounding by building on classical standardization methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where new estimators were developed to overcome the limitations of the previous estimators (ie, nonparametric and parametric g-formula, inverse probability weighting, double-robust, and data-adaptive estimators). We illustrate the implementation of different methods using an empirical example from the Connors study based on intensive care medicine, and most importantly, we provide reproducible and commented code in Stata, R, and Python for researchers to adapt in their own observational study. The code can be accessed at https://github.com/migariane/Tutorial_Computational_Causal_Inference_Estimators. [ABSTRACT FROM AUTHOR]

Objective: Multiple trials have demonstrated the metabolic effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors in patients regardless of diabetes status, and recent trials have been conducted on the combined sodium/glucose cotransporter 1 and sodium/glucose cotransporter 2 (SGLT1/SGLT2) inhibitors. Therefore, a meta-analysis was conducted to investigate the weight reduction effects and dose-response relationship of SGLT inhibitors and to assess the relative efficacy of SGLT1/SGLT2 inhibitors.Methods: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020.Results: In total, 116 randomized-controlled trials were included, with a combined cohort of 98,497 patients. Overall, patients had a mean weight reduction of -1.79 kg (95% CI: -1.93 to -1.66, p < 0.001) compared with placebo. This effect was observed across diabetes status, duration of follow-up, various comorbidities, and all SGLT drug types. Mean BMI changes were -0.71 kg/m2 (95% CI: -0.94 to -0.47, p < 0.001) compared with placebo. Canagliflozin, empagliflozin, sotagliflozin, and licogliflozin showed a dose-response relationship for mean weight change. Compared with SGLT2 inhibitors, SGLT1/SGLT2 inhibitors had a significantly larger reduction in weight.Conclusions: SGLT inhibitors demonstrated weight reduction benefits in this meta-analysis. Further studies are needed to clarify their role in weight management. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to test the efficacy of self-monitoring and feedback (SM+FB) versus SM without FB (SM) in a behavioral weight-loss intervention at 6 months.Methods: This was a randomized clinical trial. Eligibility criteria included the following: ≥18 years of age, BMI ≥ 27 and ≤43, smartphone user, and ability to engage in moderate physical activity. All participants received a 90-minute 1:1 counseling session, a Fitbit Charge 2, and a digital scale for SM. SM+FB participants were provided access to a customized smartphone application that provided three daily FB messages. The primary outcome was percentage of weight change from 0 to 6 months.Results: The sample (N = 502) was 45 (SD 14.4) years old, BMI was 33.7 (SD 4.00) kg/m2 , 79.5% of participants were female (n = 399), and 84.3% were White (n = 423). At 6 months, there was 85.86% retention and a significant percentage of weight change in both groups (SM+FB: -3.16%, 95% CI: -3.85% to -2.47%, p < 0.0001; SM: -3.20%, 95% CI: -3.86% to -2.54%, p < 0.0001) but no significant between-group mean difference (-0.04%, 95% CI: -0.99% to 0.91%, p = 0.940). A ≥5% weight loss was achieved by 31.9% of the SM+FB group and 28.3% of the SM group.Conclusions: There was no significant between-group difference in weight loss at 6 months. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test whether the Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention, delivered to parents of firstborn children, is associated with the BMI of first- and second-born siblings during infancy.Methods: Participants included 117 firstborn infants enrolled in a randomized controlled trial and their second-born siblings enrolled in an observation-only ancillary study. The RP curriculum for firstborn children included guidance on feeding, sleep, interactive play, and emotion regulation. The control curriculum focused on safety. Anthropometrics were measured in both siblings at ages 3, 16, 28, and 52 weeks. Growth curve models for BMI by child age were fit.Results: Second-born children were delivered 2.5 (SD 0.9) years after firstborns. Firstborn and second-born children whose parents received the RP intervention with their first child had BMI that was 0.44 kg/m2 (95% CI: -0.82 to 0.06) and 0.36 kg/m2 (95% CI: -0.75 to 0.03) lower than controls, respectively. Linear and quadratic growth rates for BMI for firstborn and second-born cohorts were similar, but second-born children had a greater average BMI at 1 year of age (difference = -0.33 [95% CI: -0.52 to -0.15]).Conclusions: A RP educational intervention for obesity prevention delivered to parents of firstborns appears to spill over to second-born siblings. [ABSTRACT FROM AUTHOR]

Albuminuria and estimated glomerular filtration rate (e-GFR) are early markers of renal disease and cardiovascular outcomes in persons with diabetes. Although body composition has been shown to predict systolic blood pressure, its application in predicting albuminuria is unknown. In this study, we have used machine learning methods to assess the risk of albuminuria in persons with diabetes using body composition and other determinants of metabolic health. This study is a comparative analysis of the different methods to predict albuminuria in persons with diabetes mellitus who are older than 40 years of age, using the LOOK AHEAD study cohort-baseline characteristics. Age, different metrics of body composition, duration of diabetes, hemoglobin A1c, serum creatinine, serum triglycerides, serum cholesterol, serum HDL, serum LDL, maximum exercise capacity, systolic blood pressure, diastolic blood pressure, and the ankle-brachial index are used as predictors of albuminuria. We used Area under the curve (AUC) as a metric to compare the classification results of different algorithms, and we show that AUC for the different models are as follows: Random forest classifier-0.65, gradient boost classifier-0.61, logistic regression-0.66, support vector classifier -0.61, multilayer perceptron -0.67, and stacking classifier-0.62. We used the Random forest model to show that the duration of diabetes, A1C, serum triglycerides, SBP, Maximum exercise Capacity, serum creatinine, subtotal lean mass, DBP, and subtotal fat mass are important features for the classification of albuminuria. In summary, when applied to metabolic imaging (using DXA), machine learning techniques offer unique insights into the risk factors that determine the development of albuminuria in diabetes. [ABSTRACT FROM AUTHOR]

This article presents ethnographic research with in situ seed savers and seed activists in London. Unpicking the knotty relations between kinship, place, and generation among seed savers and their seeds, this article focuses on how the intrinsic and extrinsic get woven through generations and how the situ or environment of an entity is (and is not) recognized in its identity and multispecies kin relations. I argue that thinking about seeds and the worlds in which they grow suggests that they are not only embedded in their environments, but also embody their environments. If seeds bring with them their worlds, then they are inherently malleable, so seed savers are concerned about how commercial seed breeding and ex situ conservation denatures seeds' embodied relationships with their environments and, with that, their inherent intergenerational malleability. [seed saving, multispecies kinship, generation, environment]. [ABSTRACT FROM AUTHOR]

Microbiome science considers human beings supraorganisms: single ecological units made up of symbiotic assemblages of human cells and microorganisms. Microbes co-evolve with humans, and microbial populations in human bodies are determined by environments/exposures including family, food and place, health care, race and gender inequities, and toxic pollution. Microbiomes are transgenerational links, disarrangements between different bodies and the outside world. This article asserts that microbes are kin-kin that are made of and making environments, across generations. Post/nonhuman theories have debated the agency, sociality, and ontologies of microbes and things like microbes, all the while appropriating and eliding Indigenous scholarship that directly address the nonhuman world. Microbial kin evokes Indigenous formulations that necessitate reciprocal, ethical accountability to more-than-human relations. This article uses fieldwork in a transnational microbiome malnutrition project in Bangladesh to explore what develops for both the biological and social sciences if we call human-microbe relations kinships, and call microbes our kin. [ABSTRACT FROM AUTHOR]