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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.
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.
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.
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.
This study directly compares the effectiveness of aripiprazole once-monthly 400 mg (AOM) and paliperidone palmitate once-monthly (PP) on the validated and symptom-focused Heinrichs-Carpenter Quality-of-Life Scale (QLS) in schizophrenia.
A 28-week, randomized, open-label rater-blinded, head-to-head study (NCT01795547) of AOM and PP in adult patients (18-60 years) needing a change from current oral antipsychotic treatment for any reason. The study comprised oral conversion, initiation of AOM or PP treatment according to labels, and treatment continuation with injections every 4 weeks. The primary endpoint assessed non-inferiority and subsequently superiority on change from baseline to week 28 in QLS total score analyzed using a mixed model for repeated measurements.
Of 295 randomized patients, 100/148 (67.6%) of AOM and 83/147 (56.5%) of PP patients completed 28 weeks of treatment. In treated patients, adverse events (AEs) were the most frequent reason for discontinuation; AOM: 16/144 (11.1%), PP: 27/137 (19.7%). The difference in change from baseline to week 28 on QLS total score was statistically significant (4.67 [95%CI: 0.32;9.02], p=0.036), confirming non-inferiority and establishing superiority of AOM compared to PP. The respective changes were 7.47±1.53 for AOM and 2.80±1.62 for PP. AEs occurring at rates ≥5% in either group in the treatment continuation phase were weight increased (AOM: 12/119 [10.1%]; PP: 17/109 [15.6%]), psychotic disorder (AOM: 3/119 [2.5%]; PP: 6/109 [5.5%]) and insomnia (AOM: 3/119 [2.5%]; PP: 6/109 [5.5%]).
Superior improvements on the clinician-rated QLS and lower rates of all-cause discontinuation suggest greater overall effectiveness for aripiprazole once-monthly vs paliperidone palmitate.
Computational acceleration of performance metric-based materials discovery via high-throughput screening and machine learning methods is becoming widespread. Nevertheless, development and optimization of the opto-electronic properties that depend on dilute concentrations of point defects in new materials have not significantly benefited from these advances. Here, the authors present an informatics and simulation suite to computationally accelerate these processes. This will enable faster and more fundamental materials research, and reduce the cost and time associated with the materials development cycle. Analogous to the new avenues enabled by current first-principles-based property databases, this type of framework will open entire new research frontiers as it proliferates.
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.
Background: The response of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) to Intravenous Immunoglobulins (IVIG) treatment is well established . However, determination if patients not responding to 2 IVIG treatments or those whose condition stabilizes (ICE Trial) may benefit from additional doses remains unclear. We aim to identify time period required to reach maximal strength gains from IVIG treatment. Methods: Retrospective chart review of 14 patients with CIDP was performed. Change in Grip strength (GS), Knee extension (KE), Elbow Flexion (EF) and Dorsflexion(DF) was analyzed with a dynamometer during IVIG therapy. Averages for : percent change from baseline(Max%Δ),cumulative grams(g) of IVIG and time in weeks(w) required for maximal strength recovery was determined per function (+/−SEM).Anciliary therapy for all patients was recorded. Results: Strongest improvement was observed for DF(124+/−30%,p<0.001), followed by KE(113+/−19%,p<0.01),GS(100+/−21%,p<0.001) and EF(98+/−14%p<0.05).GS improved the fastest(19.1+/−3w) followed by DF(29.5+/−7w),KE(29.6+/−4w) and EF(31+/−6w). Cumulative IVIG dose to reach Max%Δ was highest for EF(869+/−201g) and lowest for GS(573+/−78g). Conclusions: Our study has demonstrated effectiveness of multiple treatments with IVIG to reach significant improvement in strength. Different muscle groups manifested different time-dependency ,reflecting variable amounts of IVIG required. Improvement was identified to be present on a ongoing basis ,with therapy lasting between 19.1-31 weeks,requiring between 869-573g of IVIG.
Official counts of deaths attributed to disasters are often under-reported, thus adversely affecting public health messaging designed to prevent further mortality. During the Oklahoma (USA) May 2013 tornadoes, Oklahoma State Health Department Division of Vital Records (VR; Oklahoma City, Oklahoma USA) piloted a flagging procedure to track tornado-attributed deaths within its Electronic Death Registration System (EDRS). To determine if the EDRS was capturing all tornado-attributed deaths, the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) evaluated three event fatality markers (EFM), which are used to collate information about deaths for immediate response and retrospective research efforts.
Oklahoma identified 48 tornado-attributed deaths through a retrospective review of hospital morbidity and mortality records. The Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) analyzed the sensitivity, timeliness, and validity for three EFMs, which included: (1) a tornado-specific flag on the death record; (2) a tornado-related term in the death certificate; and (3) X37, the International Classification of Diseases, 10th Revision (ICD-10) code in the death record for Victim of a Cataclysmic Storm, which includes tornadoes.
The flag was the most sensitive EFM (89.6%; 43/48), followed by the tornado term (75.0%; 36/48), and the X37 code (56.2%; 27/48). The most-timely EFM was the flag, which took 2.0 median days to report (range 0-10 days), followed by the tornado term (median 3.5 days; range 1-21), and the X37 code (median >10 days; range 2-122). Over one-half (52.1%; 25/48) of the tornado-attributed deaths were missing at least one EFM. Twenty-six percent (11/43) of flagged records had no tornado term, and 44.1% (19/43) had no X37 code. Eleven percent (4/36) of records with a tornado term did not have a flag.
The tornado-specific flag was the most sensitive and timely EFM. Using the flag to collate death records and identify additional deaths without the tornado term and X37 code may improve immediate response and retrospective investigations. Moreover, each of the EFMs can serve as quality controls for the others to maximize capture of all disaster-attributed deaths from vital statistics records in the EDRS.
Issa AN, Baker K, Pate D, Law R, Bayleyegn T, Noe RS. Evaluation of Oklahoma’s Electronic Death Registration System and event fatality markers for disaster-related mortality surveillance – Oklahoma USA, May 2013. Prehosp Disaster Med. 2019;34(2):125–131
In a rational world, scientific effort would reflect society's needs. We tested this hypothesis using the area of infectious diseases, where the research response to emerging threats has obvious potential to save lives through informing interventions such as vaccination and prevention policies. Pathogens continue to evolve, emerge and re-emerge and infectious diseases that were once common become less so or their global distribution changes. A question remains as to whether scientific endeavours can adapt. Here, we identified papers on infectious diseases published in the four highest ranking, health-related journals over the 118 years from 1900. Focussing on outbreak-related and burden of disease-related metrics over the two time periods, 1990 to 2017 and 1900 to 2017, our analyses suggest that there is little underrepresentation of important infectious diseases among top ranked journals. Encouragingly our results suggest the scientific process is largely self-correcting.
The effect of small noise in a smooth dynamical system is negligible on any finite time interval; in this paper we study situations where the effect persists on intervals increasing to ∞. Such an asymptotic regime occurs when the system starts from an initial condition that is sufficiently close to an unstable fixed point. In this case, under appropriate scaling, the trajectory converges to a solution of the unperturbed system started from a certain random initial condition. In this paper we consider the case of one-dimensional diffusions on the positive half-line; this case often arises as a scaling limit in population dynamics.
Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.