Stroke Survivors Who Score below Threshold on Standard Depression Measures May Still Have Negative Cognitions of Concern

Background and Purpose— There has been an increase in screening for depression in the physically ill. We explored whether important negative cognitions may be missed by conventional approaches to screening for depression in 2 independently conducted stroke studies with similar methods. Methods— The Auckland Regional Community Stroke (ARCOS) study was a prospective, population-based stroke incidence study conducted in Auckland, New Zealand, for 12 months in 2002 to 2003. The Stroke Outcomes Study was a prospective, hospital cohort study conducted in Leeds and Bradford, United Kingdom, for 33 months in 2002 to 2005. Symptoms of abnormal mood were assessed at 6 months in ARCOS with a single simple question, “Do you often feel sad and depressed?” and the 28-item General Health Questionnaire administered as part of a structured interview and in the Stroke Outcomes Study with the 28-item General Health Questionnaire and a single question about depressed mood taken from the Present State Examination. Results— Mood data were available at 6 months from 770 ARCOS and 492 Stroke Outcomes Study participants. A significant proportion (up to 28%) of people who did not meet study criteria for depression reported important negative cognitions such as hopelessness, worthlessness, or suicidality. People who were older, dependent in activities of daily living, or not partnered were more likely to report negative cognitions. Conclusions— Important negative cognitions, including suicidal thoughts, may be missed when people are screened for depression after stroke. Screening alone is not an adequate substitute for a sensitive exploration of the psychological impact of stroke on the survivor

Klinefelters Syndrome: Change in T-Scores with Testosterone, Bisphosphonate, and Vitamin D Treatment over 6 Years

Background: Klinefelter's syndrome (KS) is characterized by extra X chromosomes and features of primary hypogonadism including osteopenia and osteoporosis. Testosterone therapy (TTh) is widely used to treat men with KS and low serum testosterone/hypogonadal symptoms, though studies on its efficacy in improving bone density show varied outcomes. Materials and Methods: We studied the effects of TTh, bisphosphonates, and vitamin D/calcium in 38 men with KS and low testosterone, hypogonadal symptoms, and T-scores consistent with osteoporosis. Our aim was to investigate at the end of follow-up (median: 87 months, range: 27-147 months), associations between age, baseline total testosterone, and T-scores, and change in T-scores after treatment. Results: At final assessment, all men had T-score values outside the osteoporotic range (-1.1 standard deviation [SD],-1.8 SD). Baseline age but not median baseline testosterone appeared associated with change in T-score and T-score at final assessment. All men had dual-energy X-ray absorptiometry every 6 months and demonstrated continued improvement in T-scores after 3 months and up to 72 months. Baseline age and T-scores (stratified by median) were associated with change in T-score at final assessment. Compared with men ≥51 years, those aged <51 years showed significantly greater improvement in T-scores between 6 and 30 months. Men with worse T-score values (<3.7 SD) showed significantly greater improvement at every time point up to 36 months. Our results indicate that TTh, bisphosphonates, and vitamin D/calcium improve osteoporosis although there is a need to better understand the effects of the individual therapies, age, and baseline T-score on treatment efficacy

A Simple PCR Method for Rapid Genotype Analysis of the TH-MYCN Transgenic Mouse

BACKGROUND: The TH-MYCN transgenic mouse is the most widely used murine model of human neuroblastoma, in which a human MYCN oncogene is targeted to neuroectodermal cells of developing mice under the influence of the rat tyrosine hydroxylase promoter. So far, homozygous transgenic mice have been identified by either Southern blot or quantitative real-time PCR. PRINCIPAL FINDINGS: To establish a simple and reliable genotyping method by conventional PCR, we confirmed the integration of the transgene in the TH-MYCN transgenic mouse by Southern blot and inverse PCR analyses. Our results showed that either five or six copies were found to be inserted in a head-to-tail tandem configuration at a single locus. The MYCN transgene/host DNA junction was sequenced and the integration site was identified at chromosome 18qE4. Finally, we succeeded in designing rapid, simple and reliable genotyping method by common PCR using primers flanking the integrated TH-MYCN transgene. CONCLUSION: We established a simple and reliable genotyping PCR method for determining the integration site of the TH-MYCN transgene that enables all possible genotypes to be distinguished within several hours. TH-MYCN mice are excellent model for human neuroblastoma study, thus our results will largely be useful for facilitating the pace of neuroblastoma study, including in the study of the tumourigenic process, and in the development of therapies to treat patients suffering from neuroblastoma

Testosterone replacement therapy: association with mortality in high-risk patient subgroups

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.[Correction added on 12 January 2024, after first online publication: Figure 1 updated in this version.]Copyright © 2023 The Authors. Objectives: We describe studies determining the association between testosterone therapy (TTh) and mortality. Materials & methods: We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk. Results: During a median follow-up interquartile range (IQR) of 114 (84–132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14–0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the “law of initial value,” where greater improvements are evident following treatment in patients with worse baseline values. Conclusions: This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.North Staffordshire Medical Institute. Grant Number: PID-200078

Disability patterns over the first year after a diagnosis of epilepsy

Objective To determine the patterns and predictors of disability over the first 12 months after a diagnosis of epilepsy. Patients and methods The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) was a prospective, multicenter, community-based study of people with newly diagnosed epilepsy in Sydney, Australia. Disability was assessed using the World Health Organization’s, Disability Assessment Schedule (WHODAS) 2.0 12-item version, at baseline (i.e. within 28 days of diagnosis) and 12 months post-diagnosis. Demographic, socioeconomic, clinical and epilepsy-related data, obtained through structured interviews, were entered into multivariable linear regression and shift analysis to determine predictors of greater disability. Results Of 259 adults (≥18 years), 190 (73%) had complete WHODAS at baseline (mean ± SD scores 4 ± 6) and follow-up (4 ± 8). After adjustment for age, sex and co-morbidity, greater overall disability at 12 months was associated with lower education (P = 0.05), economic hardship (P = 0.004), multiple antiepileptic medications (P = 0.02) and greater disability (P < 0.001) at the time of diagnosis; these variables explained 38.3% of the variance. Among the 12 WHODAS items, “being emotionally affected by health problems” was the most frequent disability problem identified at both time points (all P < 0.0001). The proportion of participants without problems in that domain improved over 12 months (from 24% to 50%, P < 0.0001), whereas the other 11 items remained relatively stable. Independent baseline predictors of a worse emotional outcome at 12 months were severe/extreme emotional distress (odds ratio [OR] 4.52, 95% confidence intervals [CI] 1.67–12.24), economic hardship (OR 2.30, 95% CI 1.24–4.25) and perceived stigma (OR 2.02, 95% CI 1.03–3.93). Conclusion Most people report problems with emotional health after a diagnosis of epilepsy but many recover over the next 12 months. Services addressing the social and psychological impact of diagnosis may be needed to improve outcome

Testosterone Therapy in Adult-Onset Testosterone Deficiency: Hematocrit and Hemoglobin Changes

Objective: Hematocrit (HCT)/hemoglobin (Hb) ratio in (%/g/dL) is around 3, with high fidelity between measured and derived Hb (applying the conversion using HCT) in various pathologies. We examined changes in HCT and Hb values and HCT/Hb, compared with baseline, in men with adult-onset testosterone deficiency (TD) given testosterone therapy (TTh). Materials and Methods: Data were analyzed from an observational, prospective registry study at various time points in 353 men with adult-onset TD receiving testosterone undecanoate (median follow-up: 105 months). After establishing baseline HCT/Hb, we compared (cf. baseline) changes in HCT, Hb, and HCT/Hb at 12, 48, 72, and 96 months. Regression analyses determined predictors of HCT and Hb change. Results: TTh was associated with ( p < 0.0001) increases in median HCT and Hb; 44% to 49% and 14.5 to 14.9 g/dL at final assessment, respectively. Regression analyses showed that HCT change was associated with baseline HCT and testosterone levels, while Hb change was associated with baseline Hb, HCT, and testosterone levels. In the total cohort and subgroups, HCT/Hb increased significantly at all time points ( p < 0.0001, cf. baseline) with over 90% of men demonstrating increases. Linear regression showed that the ratio of HCT change/Hb change (i.e., difference between HCT at the various time points and baseline value/difference between Hb at the various time points and baseline value), following TTh at each time point was higher than the baseline HCT/Hb ratio. Conclusion: HCT increase was greater than we anticipated from the established HCT/Hb of 3. We speculate that increased erythrocyte life span with associated higher Hb loss via vesiculation could account for our observation. This could have a bearing when using HbA1c as an indicator in men with adult-onset TD on TTh

Klinefelters Syndrome: Change in T-Scores with Testosterone, Bisphosphonate, and Vitamin D Treatment over 6 Years

Background: Klinefelter’s syndrome (KS) is characterized by extra X chromosomes and features of primary hypogonadism including osteopenia and osteoporosis. Testosterone therapy (TTh) is widely used to treat men with KS and low serum testosterone/hypogonadal symptoms, though studies on its efficacy in improving bone density show varied outcomes. Materials and Methods: We studied the effects of TTh, bisphosphonates, and vitamin D/calcium in 38 men with KS and low testosterone, hypogonadal symptoms, and T-scores consistent with osteoporosis. Our aim was to investigate at the end of follow-up (median: 87 months, range: 27–147 months), associations between age, baseline total testosterone, and T-scores, and change in T-scores after treatment. Results: At final assessment, all men had T-score values outside the osteoporotic range (1.1 standard deviation [SD], 1.8 SD). Baseline age but not median baseline testosterone appeared associated with change in T-score and T-score at final assessment. All men had dual-energy X-ray absorptiometry every 6 months and demonstrated continued improvement in T-scores after 3 months and up to 72 months. Baseline age and T-scores (stratified by median) were associated with change in T-score at final assessment. Compared with men ‡51 years, those aged <51 years showed significantly greater improvement in T-scores between 6 and 30 months. Men with worse T-score values (<3.7 SD) showed significantly greater improvement at every time point up to 36 months. Our results indicate that TTh, bisphosphonates, and vitamin D/calcium improve osteoporosis although there is a need to better understand the effects of the individual therapies, age, and baseline T-score on treatment efficacy

Regular breakfast consumption and type 2 diabetes risk markers in 9- to 10-year-old children in the child heart and health study in England (CHASE): a cross-sectional analysis.

BACKGROUND: Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children. METHODS AND FINDINGS: We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers. CONCLUSIONS: Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary

Testosterone Therapy: Increase in Hematocrit is Associated with Decreased Mortality

Objective: Testosterone therapy (TTh) may reduce morbidity/mortality in men with adult-onset testosterone deficiency (TD), though some cardiovascular safety concerns remain. Increased hematocrit (HCT), a recognized effect of therapy, may be associated with cardiovascular disease and mortality. We examined HCT change (Δ) in men prescribed/not prescribed testosterone, and associations with mortality. Methods: We analyzed data from a prospective registry study with adult-onset TD patients: 353 men given testosterone undecanoate (TU) and 384 opting against TTh. Change in HCT after 12, 48, 72, and 96 months of TU and at final assessment was compared (nonparametric tests). The association between baseline HCT, Δ HCT, and mortality was studied using logistic and Cox regression. Results: HCT increased significantly (median change at final assessment: +5.0%) in men on TTh. HCT was higher (p = 0.021, rank-sum test) in those alive than in those who died, although median values were identical (49.0%). Baseline HCT and Δ HCT were inversely associated with mortality after adjustment for age in both logistic and Cox regression models. Men with final HCT >49.0% (median) suffered lower mortality than men with HCT ≤49.0%. Conclusions: A median HCT increase of 5.0% was associated with TTh, mostly within 48 months of commencing therapy. An increase in HCT (up to 52.0% at final assessment) was independently associated with reduced mortality, indicating current guidelines using a HCT value of 54.0% as a threshold for management change are appropriate until further study

Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register

Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke