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Introduction: Each year, 3/1000 Canadians sustain a mild traumatic brain injury (mTBI). Many of those mTBI are accompanied by various co-injuries such as dislocations, sprains, fractures or internal injuries. A number of those patients, with or without co-injuries will suffer from persistent post-concussive symptoms (PPCS) more than 90 days post injury. However, little is known about the impact of co-injuries on mTBI outcome. This study aims to describe the impact of co-injuries on PPCS and on patient return to normal activities. Methods: This multicenter prospective cohort study took place in seven large Canadian Emergency Departments (ED). Inclusion criteria: patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of ED visit, with a Glasgow Coma Scale score of 13-15. Patients who were admitted following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. A research nurse then conducted three follow-up phone interviews at 7, 30 and 90 days post-injury, in which they assessed symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to estimate the influence of co-injuries. Results: A total of 1674 patients were included, of which 1023 (61.1%) had at least one co-injury. At 90 days, patients with co-injuries seemed to be at higher risk of having 3 symptoms ≥2 points according to the RPQ (RR: 1.28 95% CI 1.02-1.61) and of experiencing the following symptoms: dizziness (RR: 1.50 95% CI 1.03-2.20), fatigue (RR: 1.35 95% CI 1.05-1.74), headaches (RR: 1.53 95% CI 1.10-2.13), taking longer to think (RR: 1.50 95% CI 1.07-2.11) and feeling frustrated (RR: 1.45 95% CI 1.01-2.07). We also observed that patients with co-injuries were at higher risk of non-return to their normal activities (RR: 2.31 95% CI 1.37-3.90). Conclusion: Patients with co-injuries could be at higher risk of suffering from specific symptoms at 90 days post-injury and to be unable to return to normal activities 90 days post-injury. A better understanding of the impact of co-injuries on mTBI could improve patient management. However, further research is needed to determine if the differences shown in this study are due to the impact of co-injuries on mTBI recovery or to the co-injuries themselves.
Introduction: Mild traumatic brain injury (mTBI) is a serious public health issue and as much as one third of mTBI patients could be affected by persistent post-concussion symptoms (PPCS) three months after their injury. Even though a significant proportion of all mTBIs are sports-related (SR), little is known on the recovery process of SR mTBI patients and the potential differences between SR mTBI and patients who suffered non-sports-related mTBI. The objective of this study was to describe the evolution of PPCS among patients who sustained a SR mTBI compared to those who sustained non sport-related mTBI. Methods: This Canadian multicenter prospective cohort study included patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of Emergency Department (ED) visit, with a Glasgow Coma Scale score of 13-15. Patients who were hospitalized following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. Three follow-up phone interviews were conducted by a research nurse at 7, 30 and 90 days post-injury to assess symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to demonstrate the impact of the mechanism of injury (sports vs non-sports) on the presence and severity of PPCS. Results: A total of 1676 mTBI patients were included, 358 (21.4%) of which sustained a SR mTBI. At 90 days post-injury, patients who suffered a SR mTBI seemed to be significantly less affected by fatigue (RR: 0.70 (95% CI: 0.50-0.97)) and irritability (RR: 0.60 (95% CI: 0.38-0.94)). However, no difference was observed between the two groups regarding each other symptom evaluated in the RPQ. Moreover, the proportion of patients with three symptoms or more, a score ≥21 on the RPQ and those who did return to their normal activities were also comparable. Conclusion: Although persistent post-concussion symptoms are slightly different depending on the mechanism of trauma, our results show that patients who sustained SR-mTBI could be at lower risk of experiencing some types of symptoms 90 days post-injury, in particular, fatigue and irritability.
Neurocognitive impairments robustly predict functional outcome. However, heterogeneity in neurocognition is common within diagnostic groups, and data-driven analyses reveal homogeneous neurocognitive subgroups cutting across diagnostic boundaries.
To determine whether data-driven neurocognitive subgroups of young people with emerging mental disorders are associated with 3-year functional course.
Model-based cluster analysis was applied to neurocognitive test scores across nine domains from 629 young people accessing mental health clinics. Cluster groups were compared on demographic, clinical and substance-use measures. Mixed-effects models explored associations between cluster-group membership and socio-occupational functioning (using the Social and Occupational Functioning Assessment Scale) over 3 years, adjusted for gender, premorbid IQ, level of education, depressive, positive, negative and manic symptoms, and diagnosis of a primary psychotic disorder.
Cluster analysis of neurocognitive test scores derived three subgroups described as ‘normal range’ (n = 243, 38.6%), ‘intermediate impairment’ (n = 252, 40.1%), and ‘global impairment’ (n = 134, 21.3%). The major mental disorder categories (depressive, anxiety, bipolar, psychotic and other) were represented in each neurocognitive subgroup. The global impairment subgroup had lower functioning for 3 years of follow-up; however, neither the global impairment (B = 0.26, 95% CI −0.67 to 1.20; P = 0.581) or intermediate impairment (B = 0.46, 95% CI −0.26 to 1.19; P = 0.211) subgroups differed from the normal range subgroup in their rate of change in functioning over time.
Neurocognitive impairment may follow a continuum of severity across the major syndrome-based mental disorders, with data-driven neurocognitive subgroups predictive of functional course. Of note, the global impairment subgroup had longstanding functional impairment despite continuing engagement with clinical services.
Household food insecurity (HFI) is a major concern in South Asia. The pathways by which HFI may reduce child growth remain inadequately understood. In a cohort study of 12 693 maternal–infant dyads in rural Bangladesh, we examined association and likely explanatory pathways linking HFI, assessed using a validated nine-item perception-based index, to infant size at 6 months. Mothers were assessed early in pregnancy for anthropometric status, dietary diversity and socio-economic status. Infants were assessed for weight, length, and arm, chest and head circumferences and breast and complementary feeding status at birth and 6 months of age. Extent of HFI shared a negative, dose–response association with all measures of infant size at 6 months and odds of wasting and stunting; 57–89 % of variances in the unadjusted models were explained by prenatal factors (maternal nutritional status and dietary diversity), and birth size adjusted for gestational age. Postnatal infant breast and complementary feeding and morbidity exposures explained the remaining fraction of the significant association between HFI and differences in infant arm and chest circumferences and odds of underweight. Contextual (i.e. socio-economic) factors finally brought remaining non-significant fractions of the food insecurity-related mid-infancy growth deficit to practically zero. Improving food security prior to pregnancy and during gestation would likely improve infant growth the most in rural Bangladesh.
There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.
To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.
We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.
We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).
Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.
Declaration of interest
L.H. and A.A. were funded to attend the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health meetings and present review results. The authors report no other conflicts of interest.
Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
Oxidative stress is implicated in the aetiology of schizophrenia, and the antioxidant defence system (AODS) may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain and its correlates with clinical and demographic variables in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r = −0.46, p = 0.015), and a trend-level positive relationship between GSH and duration of illness (r = 0.34, p = 0.076).
Our findings are consistent with a possible compensatory upregulation of the AODS with longer duration of illness and suggest that the AODS may play a role in schizophrenia.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
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.
We assessed self-reported drives for alcohol use and their impact on clinical features of alcohol use disorder (AUD) patients. Our prediction was that, in contrast to “affectively” (reward or fear) driven drinking, “habitual” drinking would be associated with worse clinical features in relation to alcohol use and higher occurrence of associated psychiatric symptoms.
Fifty-eight Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol abuse patients were assessed with a comprehensive battery of reward- and fear-based behavioral tendencies. An 18-item self-report instrument (the Habit, Reward and Fear Scale; HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) motivations for alcohol use. To characterize clinical and demographic measures associated with habit, reward, and fear, we conducted a partial least squares analysis.
Habitual alcohol use was significantly associated with the severity of alcohol dependence reflected across a range of domains and with lower number of detoxifications across multiple settings. In contrast, reward-driven alcohol use was associated with a single domain of alcohol dependence, reward-related behavioral tendencies, and lower number of detoxifications.
These results seem to be consistent with a shift from goal-directed to habit-driven alcohol use with severity and progression of addiction, complementing preclinical work and informing biological models of addiction. Both reward-related and habit-driven alcohol use were associated with lower number of detoxifications, perhaps stemming from more benign course for the reward-related and lack of treatment engagement for the habit-related alcohol abuse group. Future work should further explore the role of habit in this and other addictive disorders, and in obsessive-compulsive related disorders.
The Pain Catastrophizing Scale (PCS) measures three aspects of catastrophic cognitions about pain—rumination, magnification, and helplessness. To facilitate assessment and clinical application, we aimed to (a) develop a short version on the basis of its factorial structure and the items’ correlations with key pain-related outcomes, and (b) identify the threshold on the short form indicative of risk for depression.
Social centers for older people.
664 Chinese older adults with chronic pain.
Besides the PCS, pain intensity, pain disability, and depressive symptoms were assessed.
For the full scale, confirmatory factor analysis showed that the hypothesized 3-factor model fit the data moderately well. On the basis of the factor loadings, two items were selected from each of the three dimensions. An additional item significantly associated with pain disability and depressive symptoms, over and above these six items, was identified through regression analyses. A short-PCS composed of seven items was formed, which correlated at r=0.97 with the full scale. Subsequently, receiver operating characteristic (ROC) curves were plotted against clinically significant depressive symptoms, defined as a score of ≥12 on a 10-item version of the Center for Epidemiologic Studies-Depression Scale. This analysis showed a score of ≥7 to be the optimal cutoff for the short-PCS, with sensitivity = 81.6% and specificity = 78.3% when predicting clinically significant depressive symptoms.
The short-PCS may be used in lieu of the full scale and as a brief screen to identify individuals with serious catastrophizing.
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
To identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children’s hospital.
Retrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.
The ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.
In total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99–15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08–18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92–19.77), or had been admitted for 31–90 days at the time of the audit (OR, 2.08; 95% CI, 1.36–3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01–1.04).
Evaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.
For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.
While previous work showed that the Centers for Disease Control and Prevention toolkit for carbapenem-resistant Enterobacteriaceae (CRE) can reduce spread regionally, these interventions are costly, and decisions makers want to know whether and when economic benefits occur.
Orange County, California
Using our Regional Healthcare Ecosystem Analyst (RHEA)-generated agent-based model of all inpatient healthcare facilities, we simulated the implementation of the CRE toolkit (active screening of interfacility transfers) in different ways and estimated their economic impacts under various circumstances.
Compared to routine control measures, screening generated cost savings by year 1 when hospitals implemented screening after identifying ≤20 CRE cases (saving $2,000–$9,000) and by year 7 if all hospitals implemented in a regional coordinated manner after 1 hospital identified a CRE case (hospital perspective). Cost savings was achieved only if hospitals independently screened after identifying 10 cases (year 1, third-party payer perspective). Cost savings was achieved by year 1 if hospitals independently screened after identifying 1 CRE case and by year 3 if all hospitals coordinated and screened after 1 hospital identified 1 case (societal perspective). After a few years, all strategies cost less and have positive health effects compared to routine control measures; most strategies generate a positive cost-benefit each year.
Active screening of interfacility transfers garnered cost savings in year 1 of implementation when hospitals acted independently and by year 3 if all hospitals collectively implemented the toolkit in a coordinated manner. Despite taking longer to manifest, coordinated regional control resulted in greater savings over time.
Environmental enteric dysfunction (EED) and systemic inflammation (SI) are common in developing countries and may cause stunting. In Bangladesh, >40 % of preschool children are stunted, but EED and SI contributions are unknown. We aimed to determine the impact of EED and SI (assessed with multiple indicators) on growth in children (n 539) enrolled in a community-based randomised food supplementation trial in rural Bangladesh. EED was defined with faecal myeloperoxidase, α-1 antitrypsin and neopterin and serum endotoxin core antibody and glucagon-like peptide-2, consolidated into gut inflammation (GI) and permeability (GP) scores, and urinary lactulose:mannitol α-1 acid glycoprotein (AGP) characterised SI. Biomarker associations with anthropometry (15-, 18- and 24-month length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) z scores) were examined in pairwise correlations and adjusted mixed-effects regressions. Stunting, wasting and underweight prevalence at 18 months were 45, 15 and 37 %, respectively, with elevated EED and SI markers common. EED and SI were not associated with 15–24-month length trajectory. Elevated (worse) GI and GP scores predicted reduced 18–24-month WLZ change (β −0·01 (se 0·00) z score/month for both). Elevated GP was also associated with reduced 15–18-month WLZ change (β −0·03 (se 0·01) z score/month) and greater 15-month WLZ (β 0·16 (se 0·05)). Higher AGP was associated with reduced prior and increased subsequent WLZ change (β −0·04 (se 0·01) and β 0·02 (se 0·00) z score/month for 15–18 and 18–24 months). The hypothesised link from EED to stunting was not observed in this sample of Bangladeshi 18-month-olds, but the effects of EED on constrained weight gain may have consequences for later linear growth or for other health and development outcomes.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
Mesoporous silicas were synthesized via a surfactant-templated sol-gel route using castor oil as the templating agent under acidic medium. The resulting silicas were subsequently amine functionalized with 3-aminopropyltriethoxysilane (NH2-MTS), [3-(2-aminoethylamino)-propyl]trimethoxysilane (NN-MTS), and [3-(diethylamino)propyl]trimethoxysilane(DN-MTS) to introduce surface basicity. Surface physicochemical properties were characterized by field emission gun scanning electron microscopy (FEGSEM), nitrogen porosimetry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and diffuse reflectance infrared fourier transform spectroscopy (DRIFTS). As-synthesised materials exhibit type IV adsorption-desorption isotherms characteristic of mesoporous structures. Clusters of spherical shaped materials were observed by FEGSEM, suggesting growth of silica occurs within colloidal dispersions. High-resolution N 1s XP spectra and DRIFT spectra confirmed the presence of amine groups in the organo-amine functionalised mesoporous silicas. The amine functionalised mesoporous silicas were active for the transesterification of tributyrin with methanol, with conversion found to increase from NH2-MTS< NN-MTS< DN-MTS.