Optima TB: A tool to help optimally allocate tuberculosis spending.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting.

Neuronal gain modulability is determined by dendritic morphology: A computational optogenetic study.

The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable. To investigate how different topologies of the neuronal dendritic tree affect the neuron's input-output characteristics we generate branching geometries which replicate morphological features of most common neurons, but keep the number of branches and overall area of dendrites approximately constant. We found a relationship between a neuron's gain modulability and its dendritic morphology, with neurons with bipolar dendrites with a moderate degree of branching being most receptive to control of the gain of their input-output relationship. The theory was then tested and confirmed on two examples of realistic neurons: 1) layer V pyramidal cells-confirming their role in neural circuits as a regulator of the gain in the circuit in addition to acting as the primary excitatory neurons, and 2) stellate cells. In addition to providing testable predictions and a novel application of dual-opsins, our model suggests that innervation of all dendritic subdomains is required for full gain modulation, revealing the importance of dendritic targeting in the generation of neuronal gain control and the functions that it subserves. Finally, our study also demonstrates that neurophysiological investigations which use direct current injection into the soma and bypass the dendrites may miss some important neuronal functions, such as gain modulation.

Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

Integrating health, nutrition, and environmental impacts of foods: a life cycle impact assessment and modelling analysis of foods in Canada.

BACKGROUND: Given the urgency of transitioning towards sustainable nutrition, dietary shifts that provide co-benefits to human health and the environment are imperative. There is currently no database of the environmental impacts of foods that reflects Canada's unique geographical and agri-climatic context and regional inputs and emissions. To determine sustainable diets, harmonising nutritional considerations with environmental impacts is also essential for an equitable comparison of foods. We aimed to develop a Canadian Food Life Cycle Inventory database and a multidimensional index to enable a joint assessment of the health and environmental impacts of foods in Canada. METHODS: The Canadian Food Life Cycle Inventory database uses life cycle assessment methodology to evaluate environmental impacts. The datasets mirror Canada's food consumption patterns, averaging the spectrum of agricultural practices weighted by domestic production and import shares. The database is structured according to the nomenclature and categorisation of the Canadian Nutrient File. Environmental sustainability is assessed using a cradle-to-grave approach, including indicators such as greenhouse gas emissions, eutrophication, particulate matter, freshwater usage, land use, non-renewable energy consumption, and food loss and waste. Environmental impacts are quantified through an environmental impact score (EIS) assigned to each impact category for a given food. The EIS-nutrition (EIS-N) integrates the evaluation of nutritional quality with environmental impacts using Nutri-Score, a validated food nutrient-profiling tool. The EIS-N is modelled as a ratio of the EIS to the Nutri-Score values. FINDINGS: Preliminary results show the greatest environmental impacts for animal-based foods, particularly beef, in agreement with current literature. Foods with greater nutritional quality also generally show greater environmental sustainability, with some exceptions for particular impact categories. INTERPRETATION: The database and index have potential to serve as powerful tools to support researchers, policy makers, and consumers, harnessing big data to drive efficient food and climate solutions for systems transformation. FUNDING: Province of Ontario and University of Toronto, CIHR SMART Healthy Cities Training Platform, and University of Toronto's Temerty Faculty of Medicine.

Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis.

Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. Data Extraction and Synthesis: Data were pooled using random-effects models and presented as ß coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45 851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268 095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.

Differences between midvastus and subvastus TKA surgical approaches in the tasks of sitting and standing.

The mini-midvastus (MV) approach to total knee arthroplasty (TKA) minimizes damage to the extensor mechanism; however, the mini-subvastus (SV) approach is designed to avoid such damage. Quadriceps weakness following TKA can have a significant impact on the activities of daily living, particularly stand-to-sit down (STSD) and sit-to-stand up (STSU) activities. Fifty-three subjects diagnosed with primary osteoarthritis and scheduled to undergo TKA were randomized to receive an MV or SV surgical approach and were given identical postoperative orders. Compared with age-matched controls, the SV group had a quicker return of normal peak knee extension moment during STSU, whereas the MV group had a quicker return of normal movement patterns in hip, knee, and ankle parameters during STSD yet represented the higher functioning subjects as more MV subjects had difficulty completing the task as instructed. Considering both movements are required for daily living, neither surgical group was found to have a significant advantage over the other in functional outcome through 6 months post-TKA.

Differences between standard and minimally invasive parapatellar surgical approaches for total knee arthroplasty in the tasks of sitting and standing.

Minimally invasive total knee arthroplasty (TKA) aims to enhance functional recovery and minimize trauma to the knee extensor mechanism through quadriceps sparing techniques. Few have studied the effect of TKA surgical approach on activities of daily living. Stand-to-sit-down (STSD) and sit-to-stand-up (STSU) activities are challenging for patients in constrained scenarios where upper body support is limited. In this study, 60 subjects diagnosed with primary osteoarthritis undergoing TKA were randomized to receive the standard parapatellar (SP) or mini-parapatellar (MP) surgical approach performed using computer navigation. All received identical postoperative orders, hospitalization, and physical therapy. Before surgery and at 2, 4, and 6 months postoperatively, the STSD and STSU kinetics and kinematics showed differences for both groups in comparison with controls, but the two were essentially indistinguishable throughout all time points.

Sugar-sweetened beverage consumption and weight gain in children and adults: a systematic review and meta-analysis of prospective cohort studies and randomized controlled trials.

BACKGROUND: Sugar-sweetened beverages (SSBs) have been implicated in fueling the obesity epidemic. OBJECTIVES: This study aimed to update a synthesis of the evidence on SSBs and weight gain in children and adults. METHODS: MEDLINE, Embase, and Cochrane databases were searched through September 8, 2022, for prospective cohort studies and randomized controlled trials (RCTs) that evaluated intake of SSBs in relation to BMI and body weight in children and adults, respectively. Eligible interventions were compared against a noncaloric control. Study-level estimates were pooled using random-effects meta-analysis and presented as ß-coefficients with 95% CIs for cohorts and weighted mean differences (MDs) with 95% CIs for RCTs. RESULTS: We identified 85 articles including 48 in children (40 cohorts, n = 91,713; 8 RCTs, n = 2783) and 37 in adults (21 cohorts, n = 448,661; 16 RCTs, n = 1343). Among cohort studies, each serving/day increase in SSB intake was associated with a 0.07-kg/m2 (95% CI: 0.04 kg/m2, 0.10 kg/m2) higher BMI in children and a 0.42-kg (95% CI: 0.26 kg, 0.58 kg) higher body weight in adults. RCTs in children indicated less BMI gain with SSB reduction interventions compared with control (MD: -0.21 kg/m2; 95% CI: -0.40 kg/m2, -0.01 kg/m2). In adults, randomization to addition of SSBs to the diet led to greater body weight gain (MD: 0.83 kg; 95% CI: 0.47 kg, 1.19 kg), and subtraction of SSBs led to weight loss (MD: -0.49 kg; 95% CI: -0.66 kg, -0.32 kg) compared with the control groups. A positive linear dose-response association between SSB consumption and weight gain was found in all outcomes assessed. CONCLUSIONS: Our updated systematic review and meta-analysis expands on prior evidence to confirm that SSB consumption promotes higher BMI and body weight in both children and adults, underscoring the importance of dietary guidance and public policy strategies to limit intake. This meta-analysis was registered at the International Prospective Register of Systematic Reviews as CRD42020209915.

Public health benefits of shifting from hospital-focused to ambulatory TB care in Eastern Europe: Optimising TB investments in Belarus, the Republic of Moldova, and Romania.

High rates of drug-resistant tuberculosis (DR-TB) continue to threaten public health, especially in Eastern Europe. Costs for treating DR-TB are substantially higher than treating drug-susceptible TB, and higher yet if DR-TB services are delivered in hospital. The WHO recommends that multidrug-resistant (MDR) TB be treated using mainly ambulatory care, shown to have non-inferior health outcomes, however, there has been a delay to transition away from hospital-focused MDR-TB care in certain Eastern European countries. Allocative efficiency analyses were conducted for three countries in Eastern Europe, Belarus, the Republic of Moldova, and Romania, to minimise a combination of TB incidence, prevalence, and mortality by 2035. A primary focus of these studies was to determine the health benefits and financial savings that could be realised if DR-TB service delivery shifted from hospital-focused to ambulatory care. Here we provide a comprehensive assessment of findings from these studies to demonstrate the collective benefit of transitioning from hospital-focused to ambulatory TB care, and to address common regional considerations. We highlight that transitioning from hospital-focused to ambulatory TB care could reduce treatment costs by 20% in Romania, 24% in Moldova, and by as much as 40% in Belarus or almost 35 million US dollars across these three countries by 2035 without affecting quality of care. Improved TB outcomes could be achieved, however, without additional spending by reinvesting these savings in higher-impact TB diagnosis and more efficacious DR-TB treatment regimens. We found commonalities in the large portion of TB cases treated in hospital across these three regional countries, and similar obstacles to transitioning to ambulatory care. National governments in the Eastern European region should examine barriers delaying adoption of ambulatory DR-TB care and consider lost opportunities caused by delays in switching to more efficient treatment modes.

Association between adherence to plant-based dietary patterns and obesity risk: a systematic review of prospective cohort studies.

The worldwide prevalence of obesity and its comorbidities is staggering, and elevated body mass index represents a leading risk factor of death globally. Consistent evidence demonstrates a high-quality plant-based diet as an effective intervention for weight management, although it may be particularly challenging to adopt in its entirety for habitual meat consumers or individuals with especially poor-quality diets. Plant-based diets are increasingly studied using indices such as the overall plant-based diet index (PDI), healthful PDI, and unhealthful PDI, which offer more flexibility than a binary classification of vegetarianism and better facilitate translation into dietary recommendations. We summarized these recently accumulated studies to comprehensively evaluate plant-based diets in relation to obesity risk. We searched Medline, Embase, and CINAHL databases through January 2022 and identified 9 prospective adult cohorts. Reporting of results was consistent with Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines and certainty of the evidence was assessed using domains from GRADE. The PDI had a protective association with body weight gain and adiposity. Emphasis of healthful plant foods strengthened this association and emphasis of unhealthful plant foods demonstrated either a positive or null association. The certainty of the evidence was considered moderate. These findings have wide application to inform dietary interventions and sustainable policy recommendations. (Prospero ID: CRD42020198143).

White rice, brown rice and the risk of type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVE: Intake of white rice has been associated with elevated risk for type 2 diabetes (T2D), while studies on brown rice are conflicting. To inform dietary guidance, we synthesised the evidence on white rice and brown rice with T2D risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE and Cochrane databases were searched through November 2021. ELIGIBILITY CRITERIA: Prospective cohort studies of white and brown rice intake on T2D risk (≥1 year), and randomised controlled trials (RCTs) comparing brown rice with white rice on cardiometabolic risk factors (≥2 weeks). DATA EXTRACTION AND SYNTHESIS: Data were extracted by the primary reviewer and two additional reviewers. Meta-analyses were conducted using random-effects models and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using the Newcastle Ottawa Scale for prospective cohort studies and the Cochrane Risk of Bias Tool for RCTs. Strength of the meta-evidence was assessed using NutriGrade. RESULTS: Nineteen articles were included: 8 cohort studies providing 18 estimates (white rice: 15 estimates, 25 956 cases, n=5 77 426; brown rice: 3 estimates, 10 507 cases, n=1 97 228) and 11 RCTs (n=1034). In cohort studies, white rice was associated with higher risk of T2D (pooled RR, 1.16; 95% CI: 1.02 to 1.32) comparing extreme categories. At intakes above ~300 g/day, a dose-response was observed (each 158 g/day serving was associated with 13% (11%-15%) higher risk of T2D). Intake of brown rice was associated with lower risk of T2D (pooled RR, 0.89; 95% CI: 0.81 to 0.97) comparing extreme categories. Each 50 g/day serving of brown rice was associated with 13% (6%-20%) lower risk of T2D. Cohort studies were considered to be of good or fair quality. RCTs showed an increase in high-density lipoprotein-cholesterol (0.06 mmol/L; 0.00 to 0.11 mmol/L) in the brown compared with white rice group. No other significant differences in risk factors were observed. The majority of RCTs were found to have some concern for risk of bias. Overall strength of the meta-evidence was moderate for cohort studies and moderate and low for RCTs. CONCLUSION: Intake of white rice was associated with higher risk of T2D, while intake of brown rice was associated with lower risk. Findings from substitution trials on cardiometabolic risk factors were inconsistent. PROSPERO REGISTRATION NUMBER: CRD42020158466.

Refinement, reliability, and validity of the segmental assessment of trunk control.

PURPOSE: The Segmental Assessment of Trunk Control (SATCo) provides a systematic method of assessing discrete levels of trunk control in children with motor disabilities. This study refined the assessment method and examined reliability and validity of the SATCo. METHODS: After refining guidelines, 102 video recordings of the SATCo were made of 8 infants with typical development followed longitudinally from 3 to 9 months of age and 24 children with neuromotor disability with a mean age of 10 years 4 months. Eight researchers independently scored recordings. RESULTS: Intraclass correlation coefficient values for interrater reliability were more than 0.84 and 0.98 across all data sets and all aspects of control. Tests of concurrent validity with the Alberta Infant Motor Scales resulted in coefficients ranging from 0.86 to 0.88. CONCLUSION: The SATCo is a reliable and valid measure allowing clinicians greater specificity in assessing trunk control.

Comment on MaaniHessari, N.; van Schalkwyk, M.C.; Thomas, S.; Petticrew, M. Alcohol Industry CSR Organisations: What Can Their Twitter Activity Tell Us about Their Independence and Their Priorities? A Comparative Analysis. Int. J. Environ. Res. Public Health 2019, 16, 892.

We noted with concern that you published recently (12 March 2019) an article about so-called "Alcohol industry CSR Organisations", which selectively targets criticism of Drinkaware [...].

Correction to: PyPNS: Multiscale Simulation of a Peripheral Nerve in Python.

The original version of this article unfortunately contained a mistake. The following text: "This project has received funding from European Research Council (ERC) Synergy Grant no. 319818." is missing in the Acknowledgments.

PyPNS: Multiscale Simulation of a Peripheral Nerve in Python.

Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms. To reduce experimentation load and allow for a faster, more detailed analysis of peripheral nerve stimulation and recording, computational models incorporating experimental insights will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealised extracellular space models in one environment. We modelled the extracellular space as a three-dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed in finite element models for different media (homogeneous, nerve in saline, nerve in cuff) and imported into our simulator. Axons, on the other hand, were modelled more abstractly as one-dimensional chains of compartments. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibres, we adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibres along the nerve with a variable tortuosity fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity alters recorded signal shapes and increases stimulation thresholds. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.

Accuracy of alcohol and breast cancer risk information on Drinkaware's website.

A recent paper in Drug and Alcohol Review analysed the information on cancer disseminated by 27 alcohol industry funded organisations. The independent UK alcohol education charity Drinkaware was among the organisations whose information was studied, and based on the analysis claims were made of misrepresentation of evidence about the alcohol-related risk of cancer and alcohol industry influence. This commentary challenges the validity of these findings in respect to the evidence relating to the Drinkaware information, as the analysis is found to be misrepresenting the information by both disregarding the wider information content provided and the order and prominence with which alcohol-related cancer risk is presented. Furthermore, it is argued that the public has a right to be provided with relevant evidence-based information about cancer risk. It is critical that Drinkaware's important public health function is not compromised by unjustified allegations of inaccuracy and by unwarranted attacks on its independence and integrity.

Hypokalaemia following paracetamol overdose in two teenage girls.

We report on two teenage girls presenting following significant paracetamol overdoses (>28 g paracetamol). Both presented within 4 h of the overdose and both were treated with N-acetylcysteine, in accordance with the National Poisons Information Service protocol. Within 8 h of presentation both had developed significant hypokalaemia with serum potassium concentrations <3.0 mmol/L and were treated with intravenous potassium chloride. Potassium concentrations returned to within reference limits (>3.5 mmol/L) after commencing potassium chloride supplementation. An audit of potassium concentrations in 254 patients presenting with significant paracetamol overdose (paracetamol >0.5 mmol/L) admitted through four A&E departments in the West of Scotland showed a significant decline in mean serum potassium from 3.9 mmol/L on admission to 3.6 mmol/L (P = <0.001) over the next 36 h. The mechanism for this hypokalaemia in these two individuals is unclear, however regular monitoring of potassium is advocated in such patients during their initial treatment.