Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, ...the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.
...emerging data on readmission programmes reinforce this worry. Without careful human interception of machine outputs and reflection on patients’ values, a machine-driven label of “nearing death” ...might lead to a subtle push towards hospice referral, rather than rehabilitative treatment—such as in the case of Ms A. By refocusing attention on the power dynamics at work behind the allure of technological certainty, social science can help clinicians maintain the fundamentally human foundation of palliative care and thereby find ways to implement these useful technologies responsibly for each patient. Instead of focusing on mortality prediction, machine learning model developers could focus on identifying patients at risk of worsening serious illness, including functional decline, deteriorating quality of life, escalating obligations for caregivers, or risk of psychosocial or spiritual distress. ...we could ask what types of technologies could be developed or applied to assist clinicians in discerning patients’ and families’ priorities and goals of care, guiding them through the conversations that are central to palliative care.
Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with ...histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.
OBJECTIVE: To investigate the prevalence of polycystic ovary syndrome (PCOS) in adolescents and its association with obesity. DESIGN: Cross-sectional study using electronic medical records. SETTING: ...Not applicable. PATIENT(S): Adolescents aged 15–19 years (n = 137,502). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): PCOS diagnosed or defined according to National Institutes of Health (NIH) criteria. RESULT(S): The prevalence of a confirmed diagnosis of PCOS was 0.56%, which increased to 1.14% when undiagnosed cases with documented symptoms qualifying for PCOS according to NIH criteria were included. Compared with normal/underweight girls, the odds ratios (OR and 95% confidence interval CI) for confirmed PCOS diagnosis were 3.85 (3.04–4.88), 10.25 (8.16–12.84), and 23.10 (18.66–28.61) for overweight, moderately obese, and extremely obese adolescents, respectively, after adjusting for potential confounders. When adolescents with two or more supportive diagnoses were included (diagnosed and undiagnosed PCOS-NIH), the ORs (95% CI) for PCOS-NIH by weight class were significantly attenuated to 2.95 (2.53–3.44), 6.73 (5.78–7.83), and 14.65 (12.73–16.86) for overweight, moderately obese, and extremely obese adolescents, respectively. CONCLUSION(S): Overweight and obesity were associated with higher odds of PCOS in adolescents. Studies based solely on diagnosis codes may underestimate the prevalence of PCOS and overestimate the magnitude of the association between obesity and PCOS.
This article presents crucial new evidence that prisons with a higher proportion of the area within their perimeter given over to natural vegetation exhibit lower levels of self-harm and violence ...(both between prisoners and toward staff). Extending prior qualitative prison-level studies that find that nature contact influences prisoners' self-reported well-being, it uses geographic information systems mapping to generate a new prison greenspace data set, capturing-for a cross section of prisons in England and Wales-the percentage of greenspace within their perimeters. Econometric estimations confirm that greenspace fosters prisoner well-being, in that there are lower levels of self-harm and violence in prisons with more greenspace. These relationships are statistically robust, and they persist when we control for prison size, type, age, and level of crowding. These findings are noteworthy in that they both extend understandings of well-being in custodial environments and have the potential to significantly influence future prison design. The article also provides important new insights demonstrating links between greenspace and well-being that have significance beyond the specifics of carceral environments.
Objective To estimate the magnitude of the association between overweight, moderate, and extreme childhood obesity and the risk of idiopathic intracranial hypertension (IIH). Study design Risk ...estimates were obtained from the Kaiser Permanente Southern California Children's Health Study (n = 913 178). Weight classes were assigned by body mass index specific for age and sex. A combination of electronic database searches followed by complete medical records review was used to identify all children diagnosed with IIH between 2006 and 2009. Results We identified 78 children with IIH, the majority of whom were girls (n = 66, 84.5%), age 11-19 (n = 66, 84.5%), non-Hispanic Whites (n = 37, 47.4%), and overweight or obese (n = 57, 73.1%). The adjusted ORs and 95% CIs of IIH with increasing weight class were 1.00, 3.56 (1.72-7.39), 6.45 (3.10-13.44), and 16.14 (8.18-31.85) for underweight/normal weight (reference category), overweight, moderately obese and extremely obese 11-19 year olds, respectively ( P for trend < .001). Other independent IIH risk factors included White non-Hispanic race/ethnicity for all age groups and female sex, but only in older children. Overweight/obese children also had more IIH symptoms at onset than normal weight children. Conclusions We found that childhood obesity is strongly associated with an increased risk of pediatric IIH in adolescents. Our findings suggest that the childhood obesity epidemic is likely to lead to increased morbidity from IIH particularly among extremely obese, White non-Hispanic teenage girls. Our findings also suggest careful screening of these at risk individuals may lead to earlier detection and opportunity for treatment of IIH.
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