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To investigate the prevalence and socioeconomic inequalities in breastmilk, breastmilk substitutes (BMS) and other non-human milk consumption, by children under two years in low- and middle-income countries (LMICs).
We analyzed the prevalence of continued breastfeeding at one and two years, and frequency of formula and other non-human milk consumption by age in months. Indicators were estimated through 24-hour dietary recall. Absolute and relative wealth indicators were used to describe within- and between-country socioeconomic inequalities.
Nationally representative surveys from 2010 onwards from 86 LMICs.
394,977 children aged under two years.
Breastfeeding declined sharply as children became older in all LMICs, especially in upper-middle income countries. BMS consumption peaked at six months of age in low/lower-middle income countries, and at around 12 months in upper-middle income countries. Irrespective of country, BMS consumption was higher in children from wealthier families, and breastfeeding in children from poorer families. Multilevel linear regression analysis showed that BMS consumption was positively associated with absolute income, and breastfeeding negatively associated. Findings for other non-human milk consumption were less straightforward. Unmeasured factors at country level explained a substantial proportion of overall variability in BMS consumption and breastfeeding.
Breastfeeding falls sharply as children become older, especially in wealthier families in upper-middle income countries; this same group also consumes more BMS at any age. Country-level factors play an important role in explaining BMS consumption by all family wealth groups, suggesting that BMS marketing at national level might be partly responsible for the observed differences.
Smoking rates in people with depression and anxiety are twice as high as in the general population, even though people with depression and anxiety are motivated to stop smoking. Most healthcare professionals are aware that stopping smoking is one of the greatest changes that people can make to improve their health. However, smoking cessation can be a difficult topic to raise. Evidence suggests that smoking may cause some mental health problems, and that the tobacco withdrawal cycle partly contributes to worse mental health. By stopping smoking, a person's mental health may improve, and the size of this improvement might be equal to taking antidepressants. In this article we outline ways in which healthcare professionals can compassionately and respectfully raise the topic of smoking to encourage smoking cessation. We draw on evidence-based methods such as cognitive–behavioural therapy (CBT) and outline approaches that healthcare professionals can use to integrate these methods into routine care to help their patients stop smoking.
The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.
How households shift spending across firms in response to income fluctuations is an important source of firm risk. Using transaction-level data, we study how households interact with the universe of retailers following income changes. We find that income increases within and across households result in substitution toward retailers in a category that are higher quality; smaller; more profitable; and have higher labor intensity, research and development (R&D) intensity, and equity betas. Although not all shifts are economically large, they do not average out across retailers. Thus, retailer choice has implications for key financial and macroeconomic outcomes, such as aggregate profitability and labor demand.
Contemporary interdependence perspectives posit that intimates are more likely to remain in a relationship to the extent that they are committed to that relationship, and that they tend to be more committed to the extent that they a) are currently satisfied with the relationship, b) believe they do not currently have more desirable alternatives to the relationship, and c) have previously invested resources into the relationship. At times, though, intimates may expect that their relationship satisfaction, alternatives, and investments will increase or decrease in the future, and research on decision-making suggests that such expectations may determine their relationship commitment more than their current or past experiences do. In this chapter, we first identify factors (e.g., plans to improve the relationship, personality, gender) that may cause intimates’ expected experiences to diverge from their current experiences. Next, we review theoretical and empirical work suggesting that intimates’ relationship commitment should be determined more by their expected experiences than by their current or past experiences. Finally, we introduce a new measure of expected relationship satisfaction, alternatives, and investments designed for future research into these ideas.
To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms.
Multicenter retrospective cohort study.
The study included 43 hospitals using a common infection prevention surveillance system.
A space–time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods.
We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals’ surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work.
Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.
Assessing impact of treatment from the patient perspective provides additional information about treatment efficacy in major depressive disorder (MDD) trials.
Pooled data from three identically designed clinical trials showed aripiprazole adjunctive to antidepressant therapy (ADT) was effective in treating MDD.1
Patients who completed an 8-week prospective ADT phase with inadequate response were randomized double-blind to 6-weeks adjunctive treatment with aripiprazole or placebo. The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) is a 16-item, self-report measure to evaluate daily functioning, with higher scores indicating better satisfaction. Comparisons of mean change from baseline (Week 8) to Week 14 in Q-LES-Q-SF items and general subscores were performed using ANCOVA (LOCF).
There was significant improvement in the Q-LES-Q-SF Overall-General subscore (total of items 1-14 expressed as a percentage of the maximum possible score) in the aripiprazole-treatment group (9.49% [n=507]) vs placebo (5.71% [n=492] p< 0.001). Placebo was significantly higher than aripiprazole in Physical Ability (placebo 0.13 vs aripiprazole 0.02, p=0.020). Aripiprazole was significantly higher than placebo in all other items except Physical Health and Vision. Aripiprazole also produced significant increases in both the Satisfaction with Medication (Item 15) (aripiprazole 0.36 vs placebo 0.20, p< 0.01) and Overall Satisfaction (Item 16) (aripiprazole 0.61 vs placebo 0.35, p< 0.001) scores.
Results emphasize that assessment of patient functioning and quality of life may have utility both in clinical trials and clinical practice.2
To evaluate the efficacy of aripiprazole adjunctive antidepressant therapy (ADT) with regard to functioning in patients with major depressive disorder (MDD) who did not achieve an adequate response with standard ADT.
Pooled data were analyzed from three nearly identically designed randomized, double-blind, placebo-controlled trials: CN138-139, CN138-163 and CN138-165. These included patients with MDD, without psychotic features, who had failed at least one ADT treatment in the present episode. Patients completing an 8-week prospective ADT phase with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole (n=508) or placebo (n=494). Functioning was assessed using the Sheehan Disability Scale (SDS). Comparisons of mean change from baseline in total SDS score, and domains of family life, social life and work/school were performed using ANCOVA.
Adjunctive aripiprazole produced significant improvements in total SDS (-1.2 on an adjusted scale of 1-10, with 10=worst level of functioning/1=best) vs adjunctive placebo (-0.7, p< 0.001). Adjunctive aripiprazole produced significant changes in the family life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001) and the social life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001). No difference between groups was observed on the work/school domain (-0.8 for adjunctive aripiprazole and -0.6 for adjunctive placebo, p=0.34).
Adjunctive aripiprazole showed significant improvements in overall SDS scores, and family and social life domains. Less change was observed in the work/school domain. The results emphasize that assessment of patient functioning may have utility both in clinical trials and clinical practice.
To evaluate dyslipidaemia risk among patients with schizophrenia treated with aripiprazole or olanzapine.
Pooled analysis of the aripiprazole clinical database, including studies of ≥7 days with at least an oral aripiprazole monotherapy arm. Mean changes from baseline to endpoint and shifts from normal to abnormal lipid levels were calculated.
Seventeen placebo- and five olanzapine-controlled studies (3 weeks->3 years) of adult patients (≥18 years) were included. Mean changes (LOCF) in lipids were similar between aripiprazole and placebo for all lipid parameters; aripiprazole showed significant improvements versus olanzapine (p≤0.01). the incidence (OC) of switching to abnormal lipid levels from baseline normal was similar between placebo and aripiprazole, and significantly lower with aripiprazole than olanzapine for most measures.
Despite limitations inherent to pooled analyses, these findings lend further support to the differential profile of atypicals, with aripiprazole showing effects on lipids comparable with placebo.
This presentation addresses impacts of adjunctive aripiprazole (AA) in major depressive disorder (MDD).
Assess impacts of long-term (≤52 weeks) open-label AA to ADT on efficacy, sexual function and weight change in MDD.
Data were analyzed post-hoc from de novo patients enrolled in an open-label safety study of AA after inadequate response to one or more ADT. Three ADT classes were included: SSRIs, SNRIs, and a noradrenaline-dopamine reuptake inhibitor, bupropion.
Global well-being with AA was assessed (mean change in CGI-S score from baseline by ADT). Sexual functioning was assessed by Sexual Function Inventory (SFI) items: interest in sex, sexual arousal, achievement of orgasm, erection maintenance and sexual satisfaction. Item 6 captured change in the overall improvement score. Weight change at Week 52 (last observation carried forward) was assessed.
Overall mean change in CGI-S (n = 285) by Week 52 was -1.5. Mean changes in CGI-S from baseline scores (4.2-4.4) were: escitalopram (n=64) -1.5, venlafaxine XL (n = 48) -1.4, sertraline (n = 39) -1.7, fluoxetine (n = 41) -1.3, paroxetine or CR (n = 37) -1.5 and bupropion XL or SR (n = 46) -1.4. Improvements on SFI items (n = 155) ranged from -0.2 (sexual satisfaction) to -0.6 (interest in sex and orgasm). Mean overall improvement score (3.8) indicated mild-to-moderate sexual dysfunction. All AA groups experienced a mean weight increase (range +1.8 kg [sertraline] to +3.3 kg [fluoxetine]).
AA moderately improved CGI-S scores (to a similar degree) when added to three different classes of ADTs. Sexual functioning in patients on ADT modestly improved after adding aripiprazole to ADT.
Evaluate the safety and tolerability of aripiprazole once-monthly (ARI-OM) initiation in patients stabilized on oral antipsychotics other than aripiprazole. Previous pivotal Phase III trials have evaluated initiating ARI-OM in patients stabilized on oral aripiprazole1.
Eligible patients were treated with oral atypical antipsychotics other than aripiprazole with a history of oral aripiprazole tolerability. The study included a screening phase (30 days) and a treatment phase (28 days). Patients were stabilized per investigator's judgment for ≥14 days on risperidone, olanzapine, quetiapine, or ziprasidone, before administration of ARI-OM (400 mg). Current oral antipsychotic was co-administered with ARI-OM for 2 weeks to determine safety and tolerability of a single ARI-OM dose following treatment initiation. Safety assessments were adverse events (AEs); extrapyramidal symptoms (EPSs) using standard objective rating scales; Columbia-Suicide Severity Rating Scale; clinical laboratory measures; and weight changes.
60 patients initiated ARI-OM, while continuing treatment for ≤2 weeks with oral risperidone (n=24), quetiapine (n=28), ziprasidone (n=5) or olanzapine (n=3). Treatment-emergent (TE) AEs (≥5%) were fatigue, injection-site pain, and restlessness (risperidone); insomnia, dystonia, injection-site pain, and toothache (quetiapine); and muscle spasm, tooth abscess, and toothache (ziprasidone). Prior olanzapine did not cause any AEs. Incidence of TE-EPSs were similar in all groups (< 5%). There were no unusual changes in objective EPS rating scales, suicidality, weight, laboratory values or fasting metabolic parameters across all groups.
The AE profile of patients receiving ARI-OM concomitant with oral atypical antipsychotics other than aripiprazole was consistent with prior reports1.
To evaluate efficacy and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, in obese (BMI =30kg/m2) and non-obese (BMI <30kg/m2) patients with schizophrenia.
Data from a 38-week, double-blind, active-controlled, non-inferiority study (NCT00706654); randomisation (2:2:1) to AOM-400mg, oral aripiprazole (10-30mg/day) (ARI), or aripiprazole once-monthly 50mg (AOM-50mg) assessing the efficacy and safety of AOM in patients requiring chronic antipsychotic treatment were used for this post-hoc analysis. We report the overall relapse rates in the 38-week randomized phase. Comparisons of overall relapse rates were analyzed using the Chi-squared test.
662 patients were randomized to: AOM-400mg (n=265); ARI (n=266); or AOM-50mg (n=131). Of these, the following were obese: AOM- 400mg: n=95; ARI: n=95; AOM-50mg: n=43. In the obese patients, the overall relapse rate was significantly (p=0.0012) lower with AOM-400mg (7.4%) than with AOM-50mg (27.9%). The difference between AOM-400mg and ARI (8.4%) was not significantly different. In the non-obese patients, the overall relapse was significantly (p=0.0153) lower with AOM-400mg (8.8%) than with AOM-50mg (19.3%). The difference between AOM-400mg and ARI (7.6%) was not significantly different. For patients treated with AOM-400mg, the most common TEAEs (>10% in any group) are presented in Table 1.
Injection site pain
Upper respiriatory tract infection
The efficacy and tolerability of aripiprazole once-monthly 400mg were similar in both the obese and non-obese subgroups.
Supported by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S
To evaluate the initial (3 months) all-cause discontinuation and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, stratified by previous treatment.
These two studies (NCT00705783 & NCT00706654) were double-blind, placebo- or active-controlled assessing the efficacy and safety of AOM-400mg. Detailed study designs have been reported previously (1, 2). This analysis was conducted on the pooled population in the first 3 months after initiating AOM-400mg treatment, on patients who received at least one dose of AOM-400mg. Outcome measures are reported for groups stratified by prior treatment.
During the first 3 months of treatment, discontinuation due to all-causes (except for those who discontinued due to the sponsor stopping the NCT00705783 study early after pre-specified efficacy parameters were met) as well as due to adverse events are presented in Table 1. The rates of insomnia and akathisia are shown in Table 1
Aripiprazole once-monthly 400mg appeared equally safe and effective (as measured by all cause discontinuation) in the first 3 months after initiation, regardless of treatment prior to entering trials.
Antipsychotic other than oral aripiprazole (converted) n=581
Evaluate the effectiveness of investigational aripiprazole once-monthly (ARI-OM) for maintenance treatment in schizophrenia.
Detailed methodology has been published previously1. Briefly, the study consisted of 4 phases: oral conversion to aripiprazole (Phase 1); oral aripiprazole stabilization (Phase 2); ARI-OM stabilization (Phase 3), with co-administration of oral aripiprazole for the first 2 weeks; and an ARI-OM maintenance phase (Phase 4). Effectiveness assessments included Investigator's Assessment Questionnaire (IAQ) scores, a scale that evaluates effectiveness of current treatment vs. pre-trial medication, where a negative change in score signals improvement, and Personal and Social Performance (PSP) scale scores, where negative change in score signals worsening.
710 patients entered Phase 2, 576 Phase 3 and 403 Phase 4 (ARI-OM=269, placebo once-monthly [placebo- OM]=134). Mean IAQ Total scores remained stable in Phase 2 (31.3) and Phase 3 (30.6). During Phase 4, the mean change in IAQ Total score was +1.3 for ARI-OM vs. +3.8 for placebo-OM (p< 0.0001). Mean changes in PSP Total scale scores showed improvement during Phase 2 (3.0) and Phase 3 (2.6). Mean change in PSP scores during Phase 4 showed greater functional stability with ARI-OM (−1.7) compared with placebo-OM (−6.2) (p=0.0002 vs. placebo-OM).
Improvements in effectiveness, as assessed by the IAQ and PSP Total scale scores, in the Phases 2 & 3 were maintained in Phase 4 for ARI-OM compared with placebo-OM. Treatment with ARI-OM improved symptoms, overall response to treatment and functioning.
The response of chronic inflammatory demyelinating polyneuropathy (CIDP) to intravenous immunoglobulins (IVIgs) treatment is well established. However, it remains unclear whether patients not responding to two IVIg treatments or those whose condition stabilizes (ICE trial) may benefit from additional doses. We aim to identify the time period required to reach maximal strength gains from IVIg treatment.
Retrospective chart review of 14 patients with CIDP was performed. Change in handgrip (HG), Knee extension (KE), elbow flexion, and dorsiflexion was analyzed with a dynamometer during IVIg therapy. Strength improvements in Nm or kg, cumulative grams (g) of IVIg, and time in days required for maximal strength recovery were determined per function (± standard error of the mean). Ancillary therapy was recorded for all patients.
Improvements in strength of each function were significant (p < 0.05). Earliest improvement was in HG (137.07 ± 21.23) and latest in KE (238.15 ± 38.9). Majority of patients improved by 200 days of therapy. HG required the lowest cumulative grams of IgG (561.71 ± 97.21) and KE the most (798 ± 120.7).
Our study has demonstrated the effectiveness of multiple treatments with IVIg to reach significant improvement in strength. Different muscle groups manifested different time dependency, reflecting the requirement of variable amounts of IVIg. Improvement was identified on an ongoing basis, with therapy lasting between 20.2 and 37.3 weeks, requiring between 562 and 798 g of IVIg.
A weakly nonlinear time-dependent theory for the evolution of superharmonics generated by the nonlinear self-interaction of a mode-1 internal tide in non-uniform stratification is developed and compared to numerical simulations. The forcing by the internal tide is found to excite near-pure mode-1 superharmonics whose natural frequency is moderately different from twice the internal tide frequency. Consequently, the superharmonics undergo a slow periodic growth and decay that is comparable to an acoustic ‘beat’. At low latitudes the beat frequency is smaller and the superharmonics can grow to larger amplitude, allowing for the possibility of a superharmonic cascade.
Modern humans evolved in Africa approximately 200,000 years ago (Campbell and Tishkoff 2010). As groups migrated out of Africa they underwent bottlenecks leading to sharp reductions in population size and genetic diversity (Amos and Hoffman 2010; Harpending and Rogers 2000; Ramachandran et al. 2005). To this day, African populations retain the most genetic diversity globally (Auton et al. 2015). In order to survive both within and out of Africa, early human populations had to adapt to their novel environments, including new food resources, colder climates, higher altitudes, and, especially, infectious diseases (Balaresque et al. 2007; Fumagalli et al. 2011). These adaptive requirements, facilitated by natural selection, led to an increased frequency of alleles that were beneficial in that environment. Due to the fact that these adaptive requirements were driven by local environmental pressures, some of these evolutionarily advantageous alleles display geographic and ancestral specificity, as observed in the genomes of present-day humans (Fumagalli et al. 2011).
The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.