Mental health visits and low socio-economic status in adolescence are associated with complications of Type 1 diabetes in early adulthood: a population-based cohort study.

AIM: To determine the association of mental health visits and socio-economic status in late adolescence with the risk of mortality and acute and chronic diabetes complications in early adulthood. METHODS: We conducted a population-based cohort study of individuals in Ontario, Canada, who had their 20th birthday between January 1999 and March 2015 and a diagnosis of diabetes prior to their 15th birthday, using linked administrative databases (n=8491). The main outcome was death; other outcomes were hypoglycaemia or hyperglycaemia-related hospitalizations and emergency department visits and chronic diabetes complications (dialysis, ophthalmological and macrovascular complications). RESULTS: Over the course of 59 361 person-years there were 127 deaths.. Low socio-economic status and mental health visits were both associated with a higher risk of death [hazard ratio 2.03, (95% CI 1.13 to 3.64) and 2.45 (95% CI 1.71 to 3.51), respectively]. Those with the lowest socio-economic status and a mental health visit had a higher rate of diabetes-related hospitalizations (rate ratio 4.84, 95% CI 3.64 to 6.44) and emergency department visits (rate ratio 3.15, 95% CI 1.79 to 5.54). Low socio-economic status and mental health visits were both associated with an increased risk of any chronic complication [hazard ratio 1.54 (95% CI 1.21 to 1.96) and 1.57 (95% CI 1.35 to 1.81), respectively]. CONCLUSION: We identified significant socio-economic and mental health disparities in the risk of death and acute and chronic complications in early adulthood for people with childhood-onset diabetes. Targeted interventions to prevent adverse events for these adolescents at highest risk should be evaluated.

Diabetes transition care and adverse events: a population-based cohort study in Ontario, Canada.

AIMS: To describe patterns of primary and diabetes care during transition age (17 to < 19 years) into early adulthood (age 19 to 26 years), and to evaluate the association of primary and diabetes care patterns during transition age with the risk of adverse events in early adulthood. METHODS: We conducted a population-based cohort study of individuals in Ontario, Canada who were diagnosed with diabetes aged < 15 years and who turned 17 between November 2006 and March 2011, followed until March 2015 (n = 2525). Using linked administrative databases, we examined healthcare use during: 'pre-transition-age' (15 to < 17 years), 'transition-age' (17 to < 19 years), and 'early adulthood' (19 to 26 years). The main outcomes were time to death or ketoacidosis and rate of diabetes-related admissions. The main exposures were the gap in diabetes care and primary care visits during transition age. RESULTS: There were < 6 deaths and 446 individuals (17.7%) had at least one admission for ketoacidosis during early adulthood. In all, 1188 individuals (47.0%) had a > 12-month gap in diabetes care and 241 (9.5%) had no primary care visits during transition age. A gap in diabetes care of > 12 months and no primary care visits during transition age were associated with an increased risk of ketoacidosis or death (adjusted hazard ratio 1.31, 95% CI 1.04-1.66 and adjusted hazard ratio 1.42, 95% CI 1.02-1.97, respectively). CONCLUSIONS: In Ontario, Canada, where physician and hospital-based services are universally covered, a high proportion of young adults with diabetes have insufficient care during transition age and this is associated with a higher risk of important adverse outcomes in early adulthood. Ensuring primary care involvement during transition may be a strategy to reduce morbidity.

Gut microbiome and symptoms in females with irritable bowel syndrome: a cross-sectional analysis.

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is associated with abdominal pain and stool frequency/character alterations that are linked to changes in microbiome composition. We tested whether taxa differentially abundant between females with IBS vs healthy control females (HC) are associated with daily gastrointestinal and psychological symptom severity. Participants (age 18-50 year) completed a 3-day food record and collected a stool sample during the follicular phase. They also completed a 28-day diary rating symptom intensity; analysis focused on the three days after the stool sample collection. 16S rRNA gene sequencing was used for bacterial identification. Taxon abundance was compared between IBS and HC using zero-inflated quantile analysis (ZINQ). We found that females with IBS (n = 67) had greater Bacteroides abundance (q = 0.003) and lower odds of Bifidobacterium presence (q = 0.036) compared to HC (n = 46) after adjusting for age, race, body mass index, fibre intake, and hormonal contraception use. Intestimonas, Oscillibacter, and Phascolarctobacterium were more often present and Christensenellaceae R-7 group, Collinsella, Coprococcus 2, Moryella, Prevotella 9, Ruminococcaceae UCG-002, Ruminococcaceae UCG-005, and Ruminococcaceae UCG-014 were less commonly present in IBS compared to HC. Despite multiple taxon differences in IBS vs HC, we found no significant associations between taxon presence or abundance and average daily symptom severity within the IBS group. This may indicate the need to account for interactions between microbiome, dietary intake, metabolites, and host factors.

Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality.

BACKGROUND: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. AIM: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. METHODS: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. FINDINGS: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2-7) vs 3 (2-5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. CONCLUSION: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality.

31P nuclear magnetic resonance evidence for the regulation of intracellular pH by Ehrlich ascites tumor cells.

The phenomenon of intracellular pH (pHin) regulation in cultured Ehrlich ascites cells was investigated using 31P nuclear magnetic resonance (NMR) spectroscopy. Measurements were made with a Bruker WH 360 wide bore NMR spectrometer at a 31P frequency of 145.78 MHz. Samples at a density of 10(8) cells ml-1 were suspended in a final volume of 2 ml of growth medium in 10 mm diameter NMR tubes. Intracellular pH was calculated from the chemical shifts of either intracellular inorganic phosphate (Piin) or intracellular 2-deoxyglucose-6-phosphate (2dG6Pin). The sugar phosphate was used as a pH probe to supplement the Piin measurements, which could not always be observed. When available, the pHin calculated from the Piin peak was identical within experimental error to the pHin calculated from the 2dG6Pin peak. Intracellular pH was measured to be more alkaline than the medium at an external pH (pHex) below 7.1. Typical values were pHin = 7.00 for pHex = 6.50. These measurements were constant for times up to 165 min using well-energized, respiring cells. This pH gradient was seen to collapse immediately upon onset of anaerobic shock. Above a pHex of 7.2 there was no significant difference between pHin and pHex. These results unequivocally demonstrate the steady state nature of the pH regulation and its dependence upon energization.

Proton magnetic resonance of transfer RNA.

The temperature dependence of the areas under the proton magnetic resonance spectra of unfractionated yeast transfer RNA in 1.0 molar NaCl is a consequence of salt-induced aggregation and does not constitute a monitor of the melting of secondary molecular structure. Such melting can be observed by following the widths of the resonances in the various regions of the spectra. Peaks attributable to dihydrouracil and the methyl groups of the methylated bases are detected in the spectra of unfractionated transfer RNA and alanine transfer RNA.

In vivo phosphorus-31 nuclear magnetic resonance reveals lowered ATP during heat shock of Tetrahymena.

Cells synthesize a characteristic set of proteins--heat shock proteins--in response to a rapid temperature jump or certain other stress treatments. The technique of phosphorus-31 nuclear magnetic resonance spectroscopy was used to examine in vivo the effects of temperature jump on two species of Tetrahymena that initiate the heat shock response at different temperatures. An immediate 50 percent decrease in cellular adenosine triphosphate was observed when either species was jumped to a temperature that strongly induces synthesis of heat shock proteins. This new adenosine triphosphate concentration was maintained at the heat shock temperature.

Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR.

The rate of net hepatic glycogenolysis was assessed in humans by serially measuring hepatic glycogen concentration at 3- to 12-hour intervals during a 68-hour fast with 13C nuclear magnetic resonance spectroscopy. The net rate of gluconeogenesis was calculated by subtracting the rate of net hepatic glycogenolysis from the rate of glucose production in the whole body measured with tritiated glucose. Gluconeogenesis accounted for 64 +/- 5% (mean +/- standard error of the mean) of total glucose production during the first 22 hours of fasting. In the subsequent 14-hour and 18-hour periods of the fast, gluconeogenesis accounted for 82 +/- 5% and 96 +/- 1% of total glucose production, respectively. These data show that gluconeogenesis accounts for a substantial fraction of total glucose production even during the first 22 hours of a fast in humans.

Cellular applications of 31P and 13C nuclear magnetic resonance.

High-resolution nuclear magnetic resonance (NMR) studies of cells and purified mitochondria are discussed to show the kind of information that can be obtained in vivo. In suspensions of Escherichia coli both phosphorus-31 and carbon-13 NMR studies of glycolysis and bioenergetics are presented. In rat liver cells the pathways of gluconeogenesis from carbon-13-labeled glycerol are followed by carbon-13 NMR. In the intact liver cells cytosolic and mitochondrial pH's were separately measured by phosphorus-31 NMR. In purified mitochondria the internal and external concentrations of inorganic phosphate, adenosine diphosphate, and adenosine triphosphate were determined by phosphorus-31 NMR while the pH difference across the membrane was measured simultaneously.

In vivo carbon-13 nuclear magnetic resonance studies of mammals.

Natural abundance carbon-13 nuclear magnetic resonances (NMR) from human arm and rat tissues have been observed in vivo. These signals arise primarily from triglycerides in fatty tissue. Carbon-13 NMR was also used to follow, in a living rat, the conversion of C-1-labeled glucose, which was introduced into the stomach, to C-1-labeled liver glycogen. The carbon-13 sensitivity and resolution obtained shows that natural abundance carbon-13 NMR will be valuable in the study of disorders in fat metabolism, and that experiments with substrates labeled with carbon-13 can be used to study carbohydrate metabolism in vivo.