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Aims Reward processing and regulation of emotions are thought to impact the development of addictive behaviors. In this study, we aimed to determine whether neural responses during reward anticipation, threat appraisal, emotion reactivity, and cognitive reappraisal predicted the transition from low-level to hazardous alcohol use over a 12-month period. Methods Seventy-eight individuals aged 18–22 with low-level alcohol use [i.e. Alcohol Use Disorder Identification Test (AUDIT) score <7] at baseline were enrolled. They completed reward-based and emotion regulation tasks during magnetic resonance imaging to examine reward anticipation, emotional reactivity, cognitive reappraisal, and threat anticipation (in the nucleus accumbens, amygdala, superior frontal gyrus, and insula, respectively). Participants completed self-report measures at 3-, 6-, 9-, and 12-month follow-up time points to determine if they transitioned to hazardous use (as defined by AUDIT scores ≥8). Results Of the 57 participants who completed follow-up, 14 (24.6%) transitioned to hazardous alcohol use. Higher baseline AUDIT scores were associated with greater odds of transitioning to hazardous use (odds ratio = 1.73, 95% confidence interval 1.13–2.66, P  = .005). Brain activation to reward, threat, and emotion regulation was not associated with alcohol use. Of the neural variables, the amygdala response to negative imagery was numerically larger in young adults who transitioned to hazardous use (g =  0.31), but this effect was not significant. Conclusions Baseline drinking levels were significantly associated with the transition to hazardous alcohol use. Studies with larger samples and longer follow-up should test whether the amygdala response to negative emotional imagery can be used to indicate a future transition to hazardous alcohol use. [ABSTRACT FROM AUTHOR]

Background: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.Research Question: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD.Study Design and Methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status.Results: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001.Interpretation: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions. [ABSTRACT FROM AUTHOR]

Background: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear.Research Question: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes?Study Design and Methods: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site.Results: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66).Interpretation: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a public health challenge worldwide, and roughly 25% of patients with diabetes in developing countries will develop at least one foot ulcer during their lifetime. The gravest outcome of an ulcerated foot is amputation, leading to premature death and larger economic costs.Methods: This study aimed to estimate the economic costs of diabetic foot in high-risk patients in Peru in 2012 and to model the cost-effectiveness of a year-long preventive strategy for foot ulceration including: sub-optimal care (baseline), standard care as recommended by the International Diabetes Federation, and standard care plus daily self-monitoring of foot temperature. A decision tree model using a population prevalence-based approach was used to calculate the costs and the incremental cost-effectiveness ratio (ICER). Outcome measures were deaths and major amputations, uncertainty was tested with a one-way sensitivity analysis.Results: The direct costs for prevention and management with sub-optimal care for high-risk diabetics is around US$74.5 million dollars in a single year, which decreases to US$71.8 million for standard care and increases to US$96.8 million for standard care plus temperature monitoring. The implementation of a standard care strategy would avert 791 deaths and is cost-saving in comparison to sub-optimal care. For standard care plus temperature monitoring compared to sub-optimal care the ICER rises to US$16,124 per death averted and averts 1,385 deaths.Conclusion: Diabetic foot complications are highly costly and largely preventable in Peru. The implementation of a standard care strategy would lead to net savings and avert deaths over a one-year period. More intensive prevention strategies such as incorporating temperature monitoring may also be cost-effective. [ABSTRACT FROM AUTHOR]

Background. Self-harm is a common reason for Emergency Department (ED) attendance. We aimed to develop a clinical tool to help identify patients at higher risk of repeat self-harm, or suicide, within 6 months of an ED self-harm presentation. Method. The tool, the ReACT Self-Harm Rule, was derived using multicentre data from a prospective cohort study. Binary recursive partitioning was applied to data from two centres, and data from a separate centre were used to test the tool. There were 29 571 self-harm presentations to five hospital EDs between January 2003 and June 2007, involving 18 680 adults aged ≥ 16 years. We estimated sensitivity, specificity and positive and negative predictive values to measure the performance of the tool. Results. A self-harm presentation was classified as higher risk if at least one of the following factors was present: recent self-harm (in the past year), living alone or homelessness, cutting as a method of harm and treatment for a current psychiatric disorder. The rule performed with 95% sensitivity [95% confidence interval (CI) 94-95] and 21% specificity (95% CI 21-22), and had a positive predictive value of 30% (95% CI 30-31) and a negative predictive value of 91 % (95% CI 90-92) in the derivation centres; it identified 83/92 of all subsequent suicides. Conclusions. The ReACT Self-Harm Rule might be used as a screening tool to inform the process of assessing self- harm presentations to ED. The four risk factors could also be used as an adjunct to in-depth psychosocial assessment to help guide risk formulation. The use of multicentre data helped to maximize the generalizability of the tool, but we need to further verify its external validity in other localities. [ABSTRACT FROM AUTHOR]

Consumer understanding of nutrition and health claims is a key aspect of current regulations in the European Union (EU). In view of this, qualitative and quantitative research techniques were used to investigate consumer awareness and understanding of product claims in the UK, focusing particularly on nutrition claims relating to sugars. Both research methods identified a good awareness of product claims. No added sugars claims were generally preferred to reduced sugars claims, and there was a general assumption that sweeteners and other ingredients would be added in place of sugars. However, there was little awareness of the level of sugar reduction and the associated calorie reduction in products when reduced sugars claims were made on pack. In focus groups, participants felt deceived if sugar reduction claims were being made without a significant reduction in calories. This was reinforced in the quantitative research which showed that respondents expected a similar and meaningful level of calorie reduction to the level of sugar reduction. The research also identified consumer confusion around the calorie content of different nutrients, including over-estimation of the calorie content of sugars. This is crucial to consumers' expectations as they clearly link sugar to calories and therefore expect a reduction in sugar content to deliver a reduction in calorie content. [ABSTRACT FROM AUTHOR]

BackgroundMortality, including suicide and accidents, is elevated in self-harm populations. Although risk factors for suicide following self-harm are often investigated, rarely have those for accidents been studied. Our aim was to compare risk factors for suicide and accidents.MethodA prospective cohort (n=30 202) from the Multicentre Study of Self-harm in England, 2000–2007, was followed up to 2010 using national death registers. Risk factors for suicide (intentional self-harm and undetermined intent) and accidents (narcotic poisoning, non-narcotic poisoning, and non-poisoning) following the last hospital presentation for self-harm were estimated using Cox models.ResultsDuring follow-up, 1833 individuals died, 378 (20.6%) by suicide and 242 (13.2%) by accidents. Independent predictors of both suicide and accidents were: male gender, age ⩾35 years (except accidental narcotic poisoning) and psychiatric treatment (except accidental narcotic poisoning). Factors differentiating suicide from accident risk were previous self-harm, last method of self-harm (twofold increased risks for cutting and violent self-injury versus self-poisoning) and mental health problems. A risk factor specific to accidental narcotic poisoning was recreational/illicit drug problems, and a risk factor specific to accidental non-narcotic poisoning and non-poisoning accidents was alcohol involvement with self-harm.ConclusionsThe similarity of risk factors for suicide and accidents indicates common experiences of socio-economic disadvantage, life problems and psychopathology resulting in a variety of self-destructive behaviour. Of factors associated with the accidental death groups, those for non-narcotic poisoning and other accidents were most similar to suicide; differences seemed to be related to criteria coroners use in reaching verdicts. Our findings support the idea of a continuum of premature death. [ABSTRACT FROM PUBLISHER]

We compared doxorubicin and metabolite pharmacokinetic data obtained from thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) assay of plasma samples from six patients who had been treated with doxorubicin. Duplicate 1-ml samples were extracted with chloroform: isopropanol (1:1) and assayed using a sensitive HPLC system incorporating a dual pump gradient with tetrahydrofuran as the mobile phase and fluorescence detection. Duplicate 1-ml samples from the same specimens were assayed using a modification of a previously described TLC assay. Areas under the curve for doxorubicin by HPLC (3.36 +/- 2.30 microM X h) and TLC (4.16 +/- 2.50 microM X h) were not significantly different (P = 0.5). Terminal half-life of doxorubicin by HPLC (28.0 +/- 6.98 h) and TLC (23.2 +/- 7.8) (P = 0.29) and the calculated total-body clearances by HPLC (0.55 +/- 0.29 l/min) and TLC (0.45 +/- 0.23) (P = 0.55) were not significantly different. Areas under the curve for doxorubicinol by HPLC (2.75 +/- 1.4 microM X h) and TLC (2.53 +/- 7.1 microM X h) (P = 0.73) showed no significant differences. HPLC detected a mixed 7-deoxydoxorubicinol aglycone-doxorubicin aglycone peak, 7-deoxydoxorubicin aglycone, and two nonpolar, unidentified metabolites. TLC detected the following aglycone metabolites: doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicinol aglycone, an unidentified polar metabolite, and several unidentified nonpolar metabolites. From these data we conclude that HPLC and TLC detect concentrations of doxorubicin and doxorubicinol from human plasma equally well to concentrations of 7.0 nM (4 pmol injected doxorubicin). Aglycones do circulate in human plasma at concentrations above the detection limits of both assays. Doxorubicinol aglycone, which is detected by TLC but not by HPLC, may be formed from artifactual breakdown of doxorubicinol during TLC development. Unidentified nonpolar compounds seen on HPLC and TLC may represent further doxorubicin metabolism than previously described. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.Methods: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.Results: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.Conclusions: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.). [ABSTRACT FROM AUTHOR]

Background: Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation.Methods: We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 ≥80% for ≥5 minutes and <90% for ≥10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked.Results: A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes.Conclusions: In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .). [ABSTRACT FROM AUTHOR]