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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.
In March 2017, the New Jersey Department of Health received reports of 3 patients who developed septic arthritis after receiving intra-articular injections for osteoarthritis knee pain at the same private outpatient facility in New Jersey. The risk of septic arthritis resulting from intra-articular injection is low. However, outbreaks of septic arthritis associated with unsafe injection practices in outpatient settings have been reported.
An infection prevention assessment of the implicated facility’s practices was conducted because of the ongoing risk to public health. The assessment included an environmental inspection of the facility, staff interviews, infection prevention practice observations, and a medical record and office document review. A call for cases was disseminated to healthcare providers in New Jersey to identify patients treated at the facility who developed septic arthritis after receiving intra-articular injections.
We identified 41 patients with septic arthritis associated with intra-articular injections. Cultures of synovial fluid or tissue from 15 of these 41 case patients (37%) recovered bacteria consistent with oral flora. The infection prevention assessment of facility practices identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, unsafe injection practices, and poor cleaning and disinfection practices. No additional cases were identified after infection prevention recommendations were implemented by the facility.
Aseptic technique is imperative when handling, preparing, and administering injectable medications to prevent microbial contamination.
This investigation highlights the importance of adhering to infection prevention recommendations. All healthcare personnel who prepare, handle, and administer injectable medications should be trained in infection prevention and safe injection practices.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Evidence on long-term influences of maternal vitamin B12 deficiency or concentrations on infant cognition is limited. We examined associations between maternal plasma vitamin B12 and cognitive development in 24-month-old infants. Maternal plasma vitamin B12 concentrations were measured at 26–28 weeks’ gestation; infant cognitive development was assessed with the Bayley Scales of Infant and Toddler Development-III at 24 months, for 443 mother–infant pairs from the Growing Up in Singapore Towards Healthy Outcomes cohort. Linear regressions adjusted for key confounders examined associations of maternal vitamin B12 with cognitive, receptive and expressive language, fine and gross motor subscales. Co-occurrence of maternal vitamin B12 with folate or vitamin B6 insufficiencies on child’s cognition was explored. Average maternal plasma vitamin B12 concentrations was 220·5 ± 80·5 pmol/l; 15 % and 41 % of mothers were vitamin B12 deficient (<148 pmol/l) and insufficient (148–220·9 pmol/l), respectively. Infants of mothers with vitamin B12 deficiency had 0·42 (95 % CI −0·70, −0·14) sd lower cognitive scores, compared with infants of mothers with sufficient vitamin B12. Co-occurrence of maternal vitamins B12 and B6 insufficiencies was associated with 0·37 (95 % CI −0·69, −0·06) sd lower cognitive scores in infants compared with infants of mothers sufficient in both vitamins. No significant associations were observed with other subscales. Study findings suggest the possible need to ensure adequate vitamin B12 during pregnancy. The impact of co-occurrence of maternal B-vitamins insufficiencies on early cognitive development warrants further investigation.
To determine the relationship between falls and deficits in specific cognitive domains in older adults.
An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.
United Kingdom community-based.
5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.
Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.
Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65–0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96–1.00; p = 0.05) remained significant for predicting recurrent falls.
The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.
The incidence of HIV infections in Canada has increased yearly since 2014. New cases of HIV have resulted almost exclusively from non-occupational exposures, including sexual contact and needle sharing. Appropriate HIV post-exposure prophylaxis is under-prescribed to patients who present to the emergency department after a high-risk exposure. In November of 2017, a Canadian guideline on HIV pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP) was published. The guideline presents a standardized, evidence-based approach to assessing risk for HIV transmission and prescribing HIV prophylaxis. This summary highlights the key points from the guideline that are relevant to the practice of emergency medicine in Canada.
Sufficient amino acid (AA) transport is essential to ensure the normal physiological function and growth of growing animals. The processes of AA sensing and transport in humans and murine animals, but rarely in goats, have been arousing great interest recently. This study was conducted to investigate the messenger RNA expression patterns of lysophosphatidic acid receptor 5 (LPAR5), guanine nucleotide-binding protein α-transducing 3 (GNAT3) and important partial AA transporters in digestive tracts, metabolic organs and muscles of growing goats. The results showed that these genes were widely expressed in goats, and had different expression patterns. LPAR5, GNAT3, solute carrier (SLC38A2), SLC7A7, SLC7A1 and SLC3A1 were rarely expressed in the rumen, but were highly expressed in the abomasum and intestine which are the main sites of AA absorption. GNAT3, SLC38A1, SLC38A2, SLC6A19, SLC7A7 and SLC7A1 showed comparatively high expression in the pancreas and the vital digestive glands, and the relatively high expression of these nine genes were noted in the tibialis posterior, the active muscle in energy metabolism. The correlation analysis showed that there were certain positive correlation among most genes. The current results indicate that the AA sensing and transport occur extensively in the abomasum and small intestine, metabolic organs and muscle tissues of ruminants, and that related genes have tissue specificity.
Hydrogen is an important intermediate that is produced during carbohydrate fermentation to volatile fatty acid and utilized by methanogens to produce methane in the rumen. Ruminal volatile fatty acid and dissolved methane concentrations are more than 500 times greater than dissolved hydrogen concentration. Therefore, we hypothesized that dissolved hydrogen might have a higher sensitivity in response to dietary changes compared with volatile fatty acid and dissolved methane. Using goats, we investigated the effects of increasing dietary starch content (maize replaced with wheat bran) and supplementing with rhubarb rhizomes and roots on the relationships among dissolved hydrogen, dissolved methane and other fermentation end products. The study was conducted in a replicated 4×4 Latin square with a 2×2 factorial arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration). Increased dietary starch and rhubarb supplementation did not alter volatile fatty acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g organic matter digested. However, goats fed the high-starch diet had greater dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low-starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002). In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes with starch content and rhubarb supplementation, when compared with volatile fatty acid concentrations and methane production.
The gastrointestinal tract (GIT) of animals is capable of sensing various kinds of nutrients via G-protein coupled receptor-mediated signaling transduction pathways, and the process is known as ‘gut nutrient chemosensing’. GPR40, GPR41, GPR43 and GPR119 are chemoreceptors for free fatty acids (FFAs) and lipid derivatives, but they are not well studied in small ruminants. The objective of this study is to determine the expression of GPR40, GPR41, GPR43 and GPR119 along the GIT of kid goats under supplemental feeding (S) v. grazing (G) during early development. In total, 44 kid goats (initial weight 1.35±0.12 kg) were slaughtered for sampling (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum) between days 0 and 70. The expression of GPR41 and GPR43 were measured at both mRNA and protein levels, whereas GPR40 and GPR119 were assayed at protein level only. The effects of age and feeding system on their expression were variable depending upon GIT segments, chemoreceptors and expression level (mRNA or protein), and sometimes feeding system × age interactions (P<0.05) were observed. Supplemental feeding enhanced expression of GPR40, GPR41 and GPR43 in most segments of the GIT of goats, whereas G enhanced expression of GPR119. GPR41 and GPR43 were mainly expressed in rumen, abomasum and cecum, with different responses to age and feeding system. GPR41 and GPR43 expression in abomasum at mRNA level was greatly (P<0.01) affected by both age and feeding system; whereas their expression in rumen and abomasum at protein level were different, feeding system greatly (P<0.05) affected GPR41 expression, but had no effect (P>0.05) on GPR43 expression; and there were no feeding system×age interactions (P>0.05) on GPR41 and GPR43 protein expression. The expression of GPR41 and GPR43 in rumen and abomasum linearly (P<0.01) increased with increasing age (from days 0 to 70). Meanwhile, age was the main factor affecting GPR40 expression throughout the GIT. These outcomes indicate that age and feeding system are the two factors affecting chemoreceptors for FFAs and lipid derivatives expression in the GIT of kids goats, and S enhanced the expression of chemoreceptors for FFAs, whereas G gave rise to greater expression of chemoreceptors for lipid derivatives. Our results suggest that enhanced expression of chemoreceptors for FFAs might be one of the benefits of early supplemental feeding offered to young ruminants during early development.
Dengue virus type 3 genotype III (DENV-3/III) is widely distributed in most dengue-endemic regions. It emerged in Malaysia in 2008 and autochthonously spread in the midst of endemic DENV-3/I circulation. The spread, however, was limited and the virus did not cause any major outbreak. Spatiotemporal distribution study of DENV-3 over the period between 2005 and 2011 revealed that dengue cases involving DENV-3/III occurred mostly in areas without pre-existing circulating DENV-3. Neutralisation assays performed using sera of patients with the respective infection showed that the DENV-3/III viruses can be effectively neutralised by sera of patients with DENV-3 infection (50% foci reduction neutralisation titres (FRNT50) > 1300). Sera of patients with DENV-1 infection (FRNT50 ⩾ 190), but not sera of patients with DENV-2 infection (FRNT50 ⩽ 50), were also able to neutralise the virus. These findings highlight the possibility that the pre-existing homotypic DENV-3 and the cross-reacting heterotypic DENV-1 antibody responses could play a role in mitigating a major outbreak involving DENV-3/III in the Klang Valley, Malaysia.
While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.
In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.
Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.
Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Many shorebird populations are in decline along the East Asian-Australasian Flyway. The rapid loss of coastal wetlands in the Yellow Sea, which provide critical stop-over sites during migration, is believed to be the cause of the alarming trends. The Yalu Jiang coastal wetland, a protected area in the north Yellow Sea, supports the largest known migratory staging populations of Bar-tailed Godwits Limosa lapponica (menzbieri and baueri subspecies) and Great Knots Calidris tenuirostris. Monitoring of the macrozoobenthos food for these shorebirds from 2011 to 2016 showed declines of over 99% in the densities of the bivalve Potamocorbula laevis, the major food here for both Bar-tailed Godwits and Great Knots. The loss of the bivalve might be caused by any combination of, but not limited to: (1) change in hydrological conditions and sediment composition due to nearby port construction, (2) run-off of agrochemicals from the extensive shoreline sea cucumber farms, and (3) parasitic infection. Surprisingly, the numbers of birds using the Yalu Jiang coastal wetland remained stable during the study period, except for the subspecies of Bar-tailed Godwit L. l. menzbieri, which exhibited a 91% decline in peak numbers. The lack of an overall decline in the number of bird days in Great Knots and in the peak numbers of L. l. baueri, also given the published simultaneous decreases in their annual survival, implies a lack of alternative habitats that birds could relocate to. This study highlights that food declines at staging sites could be an overlooked but important factor causing population declines of shorebirds along the Flyway. Maintaining the quality of protected staging sites is as important in shorebird conservation as is the safeguarding of staging sites from land claim. Meanwhile, it calls for immediate action to restore the food base for these beleaguered migrant shorebirds at Yalu Jiang coastal wetland.
The correlation between objective and subjective nasal obstruction is poor, and dissatisfaction rates after surgery for nasal obstruction are high. Accordingly, novel assessment techniques may be required. This survey aimed to determine patient experience and preferences for the measurement of nasal obstruction.
Prospective survey of rhinology patients.
Of 72 questionnaires distributed, 60 were completed (response rate of 83 per cent). Obstruction duration (more than one year) (χ2 = 13.5, p = 0.00024), but not obstruction severity, affected willingness to spend more time being assessed. Questionnaires (48 per cent) and nasal inspiratory peak flow measurement (53 per cent) are the most commonly used assessment techniques. Forty-nine per cent of participants found their assessment unhelpful in understanding their obstruction. Eighty-two per cent agreed or strongly agreed that a visual and numerical aid would help them understand their blockage.
Many patients are dissatisfied with current assessment techniques; a novel device with visual or numerical results may help. Obstruction duration determines willingness to undergo longer assessment.
Struggles managing conflict and hostility in adolescent social relationships were examined as long-term predictors of immune-mediated inflammation in adulthood that has been linked to long-term health outcomes. Circulating levels of interleukin-6 (IL-6), a marker of immune system dysfunction when chronically elevated, were assessed at age 28 in a community sample of 127 individuals followed via multiple methods and reporters from ages 13 to 28. Adult serum IL-6 levels were predicted across periods as long as 15 years by adolescents’ inability to defuse peer aggression and poor peer-rated conflict resolution skills, and by independently observed romantic partner hostility in late adolescence. Adult relationship difficulties also predicted higher IL-6 levels but did not mediate predictions from adolescent-era conflict struggles. Predictions were also not mediated by adult trait hostility or aggressive behavior, suggesting the unique role of struggles with conflict and hostility from others during adolescence. The implications for understanding the import of adolescent peer relationships for life span physical health outcomes are considered.
Little is known about the combined use of benzodiazepines and antidepressants in older psychiatric patients. This study examined the prescription pattern of concurrent benzodiazepines in older adults treated with antidepressants in Asia, and explored its demographic and clinical correlates.
The data of 955 older adults with any type of psychiatric disorders were extracted from the database of the Research on Asian Psychotropic Prescription Patterns for Antidepressants (REAP-AD) project. Demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Both univariate and multiple logistic regression analyses were performed.
The proportion of benzodiazepine and antidepressant combination in this cohort was 44.3%. Multiple logistic regression analysis revealed that higher doses of antidepressants, younger age (<65 years), inpatients, public hospital, major comorbid medical conditions, antidepressant types, and country/territory were significantly associated with more frequent co-prescription of benzodiazepines and antidepressants.
Nearly, half of the older adults treated with antidepressants in Asia are prescribed concurrent benzodiazepines. Given the potentially adverse effects of benzodiazepines, the rationale of benzodiazepines and antidepressants co-prescription needs to be revisited.
The effects of soluble fiber inclusion in gestation diets with varying fermentation characteristics (fermentation kinetics and short-chain fatty acids (SCFA)-profile) on lactational feed intake of sows and their piglet growth over two parities were investigated using an in vitro–in vivo methodology. After breeding, 90 multiparous Landrace sows were randomized to one of three experimental diets: the control (CON) diet, konjac flour (KF) diet or sugar beet pulp (SBP) diet. All diets had similar levels of net energy, CP, insoluble fiber and NDF, but KF and SBP diets had higher soluble fiber levels than the CON diet. During gestation, the sows were restrictively fed with three different diets, but during lactation, all the sows were similarly fed ad libitum. The three gestation diets were enzymatically hydrolyzed using pepsin and pancreatin, and enzymolyzed residues were used in in vitro fermentation. Gas and SCFA production were monitored during fermentation. After fermentation, enzymolyzed residues of KF or SBP diets resulted in higher final asymptotic gas volume than those of the CON diet. The enzymolyzed residues of KF diet were mainly part of rapidly fermented fractions, whereas those of SBP diet were mainly part of slowly fermented fractions. In addition, the acetic acid, butyric acid and total SCFA concentrations of enzymolyzed residues of KF diet were higher (P<0.01) than the control and SBP diets. In the in vivo studies, on day 90 of gestation, the KF diet sows had higher plasma SCFA concentration (P<0.05) at 4 h after feeding than the CON diet sows. Furthermore, the KF diet sows had lower plasma free fatty acid (FFA) concentration (P<0.01) at 4 h after feeding, and a lower value of homeostasis model assessment (HOMA)-insulin resistance (P<0.05), but a higher value of HOMA-insulin sensitivity (P<0.01). The KF diet sows also consumed more feed during lactation (P<0.01) and weaned significantly heavier pigs (P<0.01) than the CON diet sows. The overall results showed that the high fermentation capacity KF diet contributed to an increased lactational feed intake and improved performance of piglets in the second reproductive cycle.
The Distancing-Embracing model reserves a role for genre scripts in the hedonic valuation of negative emotion in art. Genre scripts, as defined in the target article, leave higher-level recipient intuitions out of scope. We argue that, in film genre scripts, lower-level stylistic features lend access to more complex conceptual knowledge, including pragmatic principles. The argument implies a consideration of the communicative dimension of aesthetic works, which could strengthen both factors of the Distancing-Embracing model.