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Long-term cocaine use is associated with a wide range of cognitive deficits and neuropsychiatric pathologies. Repetitive transcranial magnetic stimulation (rTMS) is an emerging therapeutic strategy that stimulates the prefrontal cortex and may improve cognitive inhibitory control and decision-making. This systematic review aimed to evaluate and synthesize evidence on the safety, effectiveness, and cost effectiveness of rTMS for the treatment of cocaine addiction.
Methods
A systematic review of the literature was carried out. The following electronic databases were searched to identify relevant studies published from inception to October 2020: MEDLINE, Embase, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, and Web of Science. Randomized controlled trials (RCTs), non-randomized controlled trials (nRCTs), case series studies, and full economic evaluations were included.
Results
A total of 12 relevant studies were identified, which included five RCTs, one nRCTs, and six case series studies. None of the studies reported data on cost effectiveness. The results indicated that rTMS reduces cocaine cravings and the number of doses consumed. No serious adverse effects were observed.
Conclusions
The ability to modulate the craving for cocaine in a specific way with non-invasive brain stimulation techniques, such as rTMS, could be a new adjunct to the behavioral treatment of addiction, especially for cocaine use where there is currently no approved pharmacological treatment. Despite the low quality of the included studies, preliminary results indicate that rTMS may reduce cocaine use and cravings. In any case, since this effect is considered moderate, future studies with larger sample sizes and longer follow up are required.
To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms.
Design:
An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used.
Setting:
Spanish older adults with metabolic syndrome (MetS).
Participants:
A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS.
Results:
Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)).
Conclusions:
According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.
Three independent analysis methods were developed to investigate the distribution of solid mass in foams analyzed by X-ray tomography with effective pixel sizes larger than the thickness of the solid network (sub-pixel conditions). Validation of the methods was achieved by a comparison with the results obtained employing high-resolution tomography for the same set of foams. The foams showed different solid mass distribution, which varied from being preferentially located on the edges, with a fraction of mass in the struts nearing 0.6, to materials in which the fraction of mass in the struts was low, under 0.15. In all cases, the accuracy of the proposed approaches was greater for materials with a higher fraction of mass in the struts. The method based on deconvolution of the attenuation probability density function yielded the closest results to the high-resolution characterizations. In contrast, analysis of the solid matrix thickness distribution after watershed segmentation, and binarization of high thickness regions (struts segmentation) required normalization through macroscopic measurements and revealed higher deviations with respect to the high-resolution results. However, segmentation-based methods allowed investigation of the heterogeneity of the fraction of mass in the struts along the sample.
The main purpose of the present work was to study neurocognitive performance of adolescents at risk for emotional difficulties. The sample included a total of 1,509 adolescents from stratified random cluster sampling. Derived from this sample, a group of high-risk (n = 92) and a comparison group (n = 92) were selected based on the short version of the Positive and Negative Affect Schedule (PANAS) for comparison on the University of Pennsylvania computerized neuropsychological test battery for children (PENN). A Multivariate analysis of covariance (MANCOVA) was performed taking the scores on the PENN as dependent variables and the two groups derived from the scores of the PANAS (at risk vs. comparison) as a fixed factor. Adolescents at high risk of presenting affectivity problems showed statistically significant differences in several different neurocognitive domains, in accuracy, λ = .820, F(9, 160,000) = 3.913, p < .01, partial η² = .180; speed, λ = .502, F(5, 88,000)= 17.493, p < .01, partial η² = .498; and efficiency, λ = .485, F(4, 89,000) = 23.599, p <.01, partial η² = .515. The high risk group showed lower neurocognitive performance than the comparison group. In addition, a positive statistically significant correlation was found between all the neurocognitive competences (p < .05). Results found in this study reveal that neurocognitive impairments can be shown in adolescents at psychometric high risk for emotional problems before transition to more severe psychological problems.
This paper presents a methodology that permits to automate binary classification using the minimum possible number of attributes. In this methodology, the success of the binary prediction does not lie in the accuracy of an algorithm but in the evaluation metrics, which give information about the goodness of fit; which is an important factor when the data batch is unbalanced. The proposed methodology assesses the possible biases in identifying one algorithm as the best performer when considering the goodness of fit of an algorithm through evaluation metrics. The dimension of data has been reduced through the cumulative explained variance. Then, the performance of six machine learning classification models has been compared through Matthew correlation coefficient (MCC), area under curve – receiver operating characteristic (ROC-AUC), and area under curve – precision-recall (AUC-PR). The results show graphically and numerically how the evaluation metrics interfere with the most optimal outcome of an algorithm. The algorithms with the best performance in terms of evaluation metrics have been random forest and gradient boosting. In the imbalanced datasets, MCC has provided better prediction results than ROC-AUC or AUC-PR. The proposed methodology is adapted to the case of bankruptcy prediction.
Cognitive and functional deterioration is common in hospital setting and occurs in 40 percent of admitted older patients. One of its main causes is physical inactivity. The objective of our health technology assessment was to assess the safety and clinical effectiveness of a structured multicomponent intervention of physical exercise (Vivifrail) for the prevention of the cognitive and functional deterioration in hospitalized patients aged 70 years or older and to estimate costs and the budgetary impact for the Spanish National Health Service.
Methods
A systematic review of available scientific literature (including experimental and observational designs) on the safety and effectiveness of Vivifrail was performed. A costing study and budgetary impact analysis of the incorporation of Vivifrail as a therapeutic alternative to standard care with a time horizon of 5 years was performed.
Results
One randomized controlled trial (RCT) (n = 370) showed positive effects of Vivifrail compared to usual care in functional capacity (mean difference (MD) = 2.20, 95% confidence interval (CI) 1.78 to 2.62), cognitive state (MD = 1.80, 95% CI 1.24 to 2.36), and quality of life (MD = 13.20, 95% CI 12.70 to 13.70). Regarding other variables, the Vivifrail increased the grip strength of the dominant hand (MD = 2.30; 95% CI = 1.79 to 2.81), verbal fluency (MD = 2.15; 95% CI = 1.56 to 2.74), performance of double tasks (MD = 0.10; 95% CI = 0.07 to 0.13), executive function (MD = −31.07; 95% CI = −49.23 to −12.91) and emotional state (MD = −2.00; 95% CI = −2.50 to −1.50).
The total cost of implementing Vivifrail in a 1,000-bed general hospital would be EUR18,000 per year (adjusted to 2020 currency), with approximately 150 patients older than 75 years benefited. This represents a cost of EUR120 per patient.
Conclusions
The Vivifrail could improve functional and cognitive capacity, although available evidence on the Vivifrail is very scarce. More well designed and executed RCT and cost-effectiveness study confirming or refuting the promising findings are needed for a new assessment.
Delirium is a prevalent syndrome in the hospital setting and the elderly are the most affected. The objective was to assess the safety, clinical effectiveness, and cost effectiveness of interventions for preventing delirium among people aged 65 years or older at hospital admission.
Methods
A systematic review of available scientific literature (randomized controlled trials) on the safety, effectiveness, and cost effectiveness of the interventions was conducted. The overall effect size for each type of intervention was estimated through a meta-analysis. A cost-effectiveness study in the context of the Spanish National Healthcare System was performed.
Results
Forty-nine studies were included for the effectiveness and safety assessment (25 on pharmacological interventions, 12 on perioperative interventions, 2 on non-pharmacological interventions, and 10 on multicomponent interventions). The following interventions reduced delirium incidence relative to usual care or placebo: hypnotics and sedatives (13 studies; risk ratio [RR] 0.54: 95% confidence interval [CI] 0.36–0.80); perioperative interventions aimed at limiting opioid use (two studies; RR 0.50, 95% CI: 0.29–0.86); controlling the intensity of general anesthesia (three studies; RR 0.77, 95% CI: 0.59–0.99); and multicomponent interventions (10 studies; RR 0.62, 95% CI: 0.54–0.72). In addition, multicomponent interventions reduced the duration (mean difference −1.18, 95% CI: −1.95 - −0.40) and severity of delirium (standardized mean difference −0.98, 95% CI: −1.46 - −0.49), while dexmedetomidine reduced the duration of delirium (mean difference −0.70, 95% CI: −1.03 - −0.37).
The economic analysis of a multicomponent preventive intervention estimated an average cost of EUR7,282 per patient, which was EUR140 per patient more expensive than usual care. The incremental cost-effectiveness ratio was EUR21,391 per quality-adjusted life-year, which is below the acceptability threshold used in Spain. The literature review yielded two economic evaluations that estimated the cost effectiveness of a multicomponent intervention in the United Kingdom and found that the multicomponent intervention was a dominant strategy.
Conclusions
This meta-analysis suggests that multicomponent interventions and dexmedetomidine are effective in reducing the incidence of delirium in hospitalized patients and that multicomponent interventions could be a cost-effective strategy in Spain.
Hepatitis A (HA) is a liver disease with a low mortality rate, but it can cause debilitating symptoms and fulminant hepatitis in some cases. Its incidence is greater in geographical areas with poor sanitation and hygiene. Spain is considered a low-endemicity country, so universal childhood immunization against HA is currently not financed by the National Health System. The aim of this study was to synthesize the scientific evidence on the cost effectiveness of universal childhood vaccination against HA.
Methods
Full economic evaluations, published in the English or Spanish languages, were included if they reported outcome measures related to the prevention of HA, adverse effects, or incremental cost-effectiveness ratios (ICERs). The Medline, Embase and Cochrane Library databases were searched for articles published from the beginning of the databases to April 2018.
Results
A total of 23 economic evaluations were included: one in a country of high endemicity, nine in countries of intermediate endemicity, and 13 in countries with low endemicity. Only one Spanish study, published in 1997, was found. Studies conducted in high- and intermediate- endemicity countries concluded that a universal childhood vaccination program against HA was a cost-effective option. However, in the case of countries with low endemicity the results were heterogeneous, although most agreed that a systematic vaccination strategy would not be a cost-effective option and that the adoption of such a strategy would not be justified given the limited benefits it would offer. The results of the economic evaluations depended on parameters such as the price and duration of the vaccine effect and the program coverage.
Conclusions
In countries with low endemicity the results were heterogeneous, although most studies concluded that the implementation of a universal vaccination strategy is not justified from the point of view of cost effectiveness.
Patients with type 1 diabetes (T1D) require the administration of insulin to maintain glycemic control. Currently, two modes of subcutaneous insulin delivery have gained wider acceptance: multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). Randomized controlled trials have shown that CSII is associated with a slightly lower glycated hemoglobin (HbA1c) level when compared with MDI.
The case study on diabetes by the H2020 Next Generation Health Technology Assessment project aims to link evidence from randomized controlled trials to real-world data to estimate the impact of health technology on specific subgroups of patients, as a first step in building prediction models to personalize treatment strategies. This work aims to assess whether patients with T1D can be stratified according to the use of health technology for insulin delivery and associated glycemic control from real-world data.
Methods
We used a longitudinal prospective data repository of T1D patients from 83 clinics in the United States (T1D exchange). A data-driven two-step clustering analysis was done on adult individuals (n = 8,034) with more than five years of disease duration. Clusters were based on body mass index (BMI), sex, age at diagnosis, diabetes duration, HbA1c level, and insulin delivery method. The optimal number of clusters was estimated based on silhouette width.
Results
We identified the following four clusters of T1D patients characterized by differences in gender and insulin delivery method: men and women with insulin injections or pens and men and women with CSII. Individuals that used CSII had lower HbA1c levels, a higher BMI, and longer diabetes duration than those using Injections or pens.
Conclusions
This preliminary work identified subgroups of T1D patients linked to insulin delivery methods. Future research includes the study of complications associated with different clusters and additional data sources. While the data were sourced from the T1D Exchange, the analyses, content, and conclusions presented have not been reviewed or approved by the T1D Exchange.
Time of flight (TOF) and energy analysis in vacuum are used in series to determine jet velocity Uj, diameter dj, electrical potential Vj and energy dissipated ΔV at the breakup point of electrified nanojets of the ionic liquid 1-Ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate (EMI-FAP) (Ignat'ev et al., J. Fluorine Chem., vol. 126, issue 8, 2008, pp.1150–1159). The full spray is periodically gated by a grid held at a high voltage Vg, and received at a collector where the measured flight times provide the distribution of drop speeds u. Varying Vg provides the bivariate distribution of drop energies ξ and velocities. The collector plate, centred with the beam axis, is divided into eight concentric rings, yielding the angular distribution of the spray current, and high resolution (u,ξ) values in the whole spray. The energies of various particles of given u are all well defined, but depend uniquely on u, even though u and ξ are in principle independent experimental variables. Slow and fast particles have energies respectively well above and below the capillary voltage Ve (1.64 kV). As previously shown by Gamero-Castaño & Hruby (J. Fluid Mech., vol. 459, 2002, pp. 245–276), this behaviour is due to the 2-stage acceleration process, first jointly in the jet for all particles, and then separately for free flying drops or ions of different mass/charge. The measured two-dimensional distributions of u and ξ provide the jet velocity Uj (~0.44 km s−1) and electrical potential Vj (1.2 kV) at the breakup point. All molecular ions originate near the breakup point rather than the meniscus neck. A measurable fraction of anomalously fast drops is observed that must come from Coulomb fissions of the main drops.
Male mating success depends on various traits and factors, and correctly identifying these traits can be key in the context of pest management. For tephritid pests, controlled through the sterile insect technique (SIT) traits, such as male size, can be manipulated through mass-rearing procedures. Thus, it is particularly important to understand whether male size can favor mating success. Here, we evaluated mating success of males of different sizes in Anastrepha ludens and Anastrepha obliqua, two species controlled through SIT. For both species, a morphometric analysis was performed of mated and unmated mass-reared and wild males in field cages. In both A. ludens and A. obliqua, wild females did not discriminate their mates based on male size and mated more frequently with wild males regardless of size. For mass-reared males, we found no evidence of an advantage of the large males compared to small males in mating success. However, we did find differences between the morphometric traits of mass-reared and wild males. In A. ludens, traits associated to mating success were Face Width (FW), Head Width (HW), Thorax Length (TL) and Wing Length (WL), and for A. obliqua were FW, HW, WL and WW (Wing Width). Overall, FW and TL were more consistent predictors of mating success. In conclusion, female choice seems to suggest multivariate selection, confirming that overall body size (expressed as pupal diameter, which is highly correlated with weight) is not a decisive factor in male mating success in these two species. However, morphological traits such as FW, HW, TL, WL and WW may be relevant in mating preference of wild female.
The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20 272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12·3 years of median follow-up (interquartile range: 6·8–15·0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (≥50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) = 2·82, 95 % CI 1·38, 5·79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1·17 (95 % CI 1·08, 1·26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose–response association with premature mortality (<65 years) in this young and highly educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.
To ascertain whether patients prescribed second generation antipsychotics for off-label indications are being monitored and screened adequately for physical health side-effects.
Background
The prevalence of off-label antipsychotic use has increased significantly over recent decades. Common off-licence uses include dementia, post-traumatic stress disorder, adjunctive treatment for unipolar depression and personality disorders. Recent studies have demonstrated that up to 65% of antipsychotic prescriptions are now off-label. Since the metabolic side-effects of second-generation antipsychotics are well-established, guidelines have emphasised the need for active, routine physical health screening of all individuals taking these drugs. However, there have been few studies or reviews which have specifically investigated screening rates of individuals receiving antipsychotic medications for off-licence indications.
Method
An audit of patients taking second-generation antipsychotics for off-label indications, under the caseload of Neighbourhoods 1, 3 and 4 of Lewisham Assessment & Liaison team, was conducted. After isolating individual patients fulfilling inclusion criteria, patient investigation documents were requested from relevant GP practices. 40 patients were isolated in total, and data were successfully collected in 60% (n = 24). Data were collected via a proforma. This consisted of patient information, indications for antipsychotic use, and each variable to be monitored. The audit standard used was the recommendations of the 12th Maudsley guidelines. Data were then entered into SPSS and analysed.
Result
The most common reasons for off-label antipsychotic prescribing were Emotionally Unstable Personality disorder (42%, n = 10) and depression (29%, n = 7). Findings demonstrated that 54% (n = 13) of patients audited had ‘basic’ blood screening (FBC, U&E, LFTs), however glucose (38%, n = 9), Prolactin (13%, n = 3), and Creatine Kinase (0%, n = 0), and monitoring was less frequent. 0% (n = 0) were completely monitored as per audit standard.
Conclusion
Primary care monitoring of off-label antipsychotics is unsatisfactory, with no patients having a complete set of investigations. Reasons for this are unclear at this stage, however based on initial discussion with GP surgeries, may be due to lack of education regarding screening investigations, patients lost between primary and secondary care services, and a lack of clarity regarding responsibility and designated roles. This audit will be expanded to also include patients from Neighbourhood 2 of the Lewisham Assessment & Liaison team. A more detailed investigation will be conducted into the barriers to physical health screening, such that a targeted intervention can be implanted.
Brucellosis remains one of the main zoonoses worldwide. Epidemiological data on human brucellosis in Spain are scarce. The objective of this study was to assess the epidemiological characteristics of inpatient brucellosis in Spain between 1997 and 2015. A retrospective longitudinal descriptive study was performed. Data were requested from the Health Information Institute of the Ministry of Health and Equality, which provided us with the Minimum Basic Data Set of patients admitted to the National Health System. We also obtained data published in the System of Obligatory Notifiable Diseases. A total of 5598 cases were registered. The period incidence rate was 0.67 (95% CI 0.65–0.68) cases per 100 000 person-years. We observed a progressive decrease in the number of cases and annual incidence rates. A total of 3187 cases (56.9%) came from urban areas. The group most at risk comprised men around the fifth decade of life. The average (±s.d.) hospital stay was 12.6 days (±13.1). The overall lethality rate of the cohort was 1.5%. The number of inpatients diagnosed with brucellosis decreased exponentially. The group of patients with the highest risk of brucellosis in our study was males under 45 years of age and of urban origin. The lethality rate has reduced to minimum values. It is probable that hospital discharge records could be a good database for the epidemiological analysis of the hospital management of brucellosis and offer a better information collection system than the notifiable diseases system (EDO in Spanish).