BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study ...involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 95% confidence interval, +0.03 to +1.68). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β standard error, −1.19 0.43 and −0.68 0.33 log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 95% confidence interval, 0.03–0.35 and 0.30 0.10–0.90 for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance
An association between diabetes and infection has been recognised for many years, with infection being an important cause of death and morbidity in people with diabetes. The COVID-19 pandemic has ...re-kindled an interest in the complex relationship between diabetes and infection. Some infections occur almost exclusively in people with diabetes, often with high mortality rates without early diagnosis and treatment. However, more commonly, diabetes is a complicating factor in many infections. A reciprocal relationship occurs whereby certain infections and their treatments may also increase the risk of diabetes. People with diabetes have a 1.5- to 4-fold increased risk of infection. The risks are the most pronounced for kidney infection, osteomyelitis and foot infection, but are also increased for pneumonia, influenza, tuberculosis, skin infection and general sepsis. Outcomes from infection are worse in people with diabetes, with the most notable example being a twofold higher rate of death from COVID-19. Hyperglycaemia has deleterious effects on the immune response. Vascular insufficiency and neuropathy, together with altered skin, mucosal and gut microbial colonisation, contribute to the increased risk of infection. Vaccination is important in people with diabetes although the efficacy of certain immunisations may be compromised, particularly in the presence of hyperglycaemia. The principles of treatment largely follow those of the general population with certain notable exceptions.
Graphical Abstract
There are no validated risk scores for predicting coronary heart disease (CHD) in Chinese patients with type 2 diabetes mellitus. This study aimed to validate the UKPDS risk engine and, if indicated, ...develop CHD risk scores. A total of 7,067 patients without CHD at baseline were analyzed. Data were randomly assigned to a training data set and a test data set. Cox models were used to develop risk scores to predict total CHD in the training data set. Calibration was assessed using the Hosmer-Lemeshow test, and discrimination was examined using the area under the receiver-operating characteristic curve in the test data set. During a median follow-up of 5.40 years, 4.97% of patients (n = 351) developed incident CHD. The UKPDS CHD risk engine overestimated the risk of CHD with suboptimal discrimination, and a new total CHD risk score was developed. The developed total CHD risk score was 0.0267 × age (years) − 0.3536 × sex (1 if female) + 0.4373 × current smoking status (1 if yes) + 0.0403 × duration of diabetes (years) − 0.4808 × Log10 (estimated glomerular filtration rate ml/min/1.73 m2 ) + 0.1232 × Log10 (1 + spot urinary albumin-creatinine ratio mg/mmol) + 0.2644 × non–high-density lipoprotein cholesterol (mmol/L). The 5-year probability of CHD = 1 − 0.9616EXP(0.9440 × RISK SCORE − 0.7082) . Predicted CHD probability was not significantly different from observed total CHD probability, and the adjusted area under the receiver-operating characteristic curve was 0.74 during 5 years of follow-up. In conclusion, the UKPDS CHD risk engine overestimated the risk of Chinese patients with type 2 diabetes mellitus and the newly developed total CHD risk score performed well in the test data set. External validations are required in other Chinese populations.
OBJECTIVE:--Chronic kidney disease (CKD) predicts cardiovascular disease (CVD) in the general population. We investigated the effects of stages of renal function using the estimated glomerular ...filtration rate (eGFR) on all-cause mortality and cardiovascular end points in a prospective cohort of Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS--Between 1995 and 2000, 4,421 patients without macrovascular disease or end-stage renal disease were recruited. Renal function was assessed by eGFR, as calculated by the abbreviated Modification of Diet in Renal Disease Study Group formula. Clinical end points included all-cause mortality, cardiovascular end point (cardiovascular death, new admissions due to angina, myocardial infarction, stroke, revascularization, or heart failure), and renal end point (reduction in eGFR by >50%, progression of eGFR to stage 5, or dialysis or renal death). RESULTS:--After a median follow-up period of 39.4 months (interquartile range 20.3-55), all-cause mortality rate increased from 1.2% (95% CI 0.8-1.7) to 18.3% (9.1-27.5) (P for trend <0.001) as renal function deteriorated from stage 1 (eGFR >=90 ml/min per 1.73 m²) to stage 4 (15-29 ml/min per 1.73 m²). The respective rate of new cardiovascular end points also increased from 2.6% (2.0-3.3) to 25.3% (15.0-35.7) (P for trend <0.001). After adjustment for covariates (age, sex, albuminuria, use of renin-angiotensin-aldosterone system RAAS inhibitors, lipids, blood pressure, and glycemic control), hazard ratios across different stages of eGFR (>=90, 60-89, 30-59, and 15-29 ml/min per 1.73 m²) for all-cause mortality were 1.00, 1.27, 2.34, and 9.82 (P for trend <0.001), for cardiovascular end points were 1.00, 1.04, 1.05, and 3.23 (P for trend <0.001), and for renal end points were 1.00, 1.36, 3.34, and 27.3 (P for trend <0.001), respectively. CONCLUSIONS:--Chinese type 2 diabetic patients with reduced eGFR were at high risk of developing cardiovascular end points and all-cause mortality, independent of albuminuria and metabolic control.
OBJECTIVE:--The purpose of this study was to compare the predictive value for coronary heart disease (CHD) of the International Diabetes Federation (IDF) definition (with Asian criteria for central ...obesity) of the metabolic syndrome with existing criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS--Subjects with type 2 diabetes and without macrovascular diseases or end-stage renal disease were categorized by the criteria of the IDF and the NCEP ATP III. CHD was defined as myocardial infarction, ischemic heart disease, coronary revascularization, heart failure, and death related to CHD. RESULTS:--Of 4,350 patients (aged 54.4 ± 13.4 years; median follow-up period 7.1 interquartile range 5.2-8.5 years), 65.9% had metabolic syndrome according to either IDF or NCEP ATP III criteria. The NCEP ATP III definition identified metabolic syndrome in 786 subjects (18.1%) who did not fulfill the criteria of the IDF. HDL cholesterol and systolic blood pressure were predictors of CHD after adjustment for other confounding factors. Compared with subjects without metabolic syndrome, the IDF criteria failed to predict CHD (hazard ratio 1.13 95% CI 0.86-1.48, P = 0.374). In contrast, the NCEP ATP III definition (2.51 1.80-3.50, P < 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 1.66-3.73, P < 0.001). CONCLUSIONS:--With established type 2 diabetes, the IDF definition of the metabolic syndrome failed to identify a subgroup of patients who had the highest risk for CHD. Practitioners must recognize the appropriate setting for its application.
Textbook of Diabetes Holt, Richard I. G; Cockram, Clive; Flyvbjerg, Allan ...
2017, 2016-12-07, 2016-12-06
eBook
Now in its fifth edition, the Textbook of Diabetes has established itself as the modern, well-illustrated, international guide to diabetes. Sensibly organized and easy to navigate, with exceptional ...illustrations, the Textbook hosts an unrivalled blend of clinical and scientific content. Highly-experienced editors from across the globe assemble an outstanding set of international contributors who provide insight on new developments in diabetes care and information on the latest treatment modalities used around the world. The fifth edition features an array of brand new chapters, on topics including: Ischaemic Heart Disease Glucagon in Islet Regulation Microbiome and Diabetes Diabetes and Non-Alcoholic Fatty Liver Disease Diabetes and Cancer End of Life Care in Diabetes as well as a new section on Psychosocial aspects of diabetes. In addition, all existing chapters are fully revised with the very latest developments, including the most recent guidelines from the ADA, EASD, DUK and NICE. Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates Via the companion website, readers can access a host of additional online materials such as: 200 interactive MCQ's to allow readers to self-assess their clinical knowledge every figure from the book, available to download into presentations fully searchable chapter pdfs Once again, Textbook of Diabetes provides endocrinologists and diabetologists with a fresh, comprehensive and multi-media clinical resource to consult time and time again.
We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios ...>3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide Scan for Metabolic Syndrome and Related Quantitative Traits in Hong Kong Chinese and Confirmation of a Susceptibility
Locus on Chromosome 1q21-q25
Maggie C.Y. Ng 1 2 ,
Wing-Yee So 1 ,
...Vincent K.L. Lam 1 ,
Clive S. Cockram 1 ,
Graeme I. Bell 2 3 4 ,
Nancy J. Cox 3 4 and
Juliana C.N. Chan 1
1 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
SAR
2 Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois
3 Department of Human Genetics, The University of Chicago, Chicago, Illinois
4 Department of Medicine, The University of Chicago, Chicago, Illinois
Address correspondence and reprint requests to Dr. Maggie C.Y. Ng, Howard Hughes Medical Institute, University of Chicago,
5841 S. Maryland Ave., MC1028, Chicago, IL 60637. E-mail: maggieng{at}uchicago.edu
Abstract
We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes
Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis
on MES. We also selected 179 families with 897 members (2,127 relative pairs) for variance component-based linkage analyses
on seven MES-related traits: waist circumference, systolic and diastolic blood pressure (BP), triglyceride, HDL cholesterol,
fasting plasma glucose, and insulin resistance index (insulin resistance index by homeostasis model assessment HOMA%IR).
Analyses revealed three regions that showed suggestive linkage for MES and also showed overlapping signals for metabolic traits:
chromosome 1 at 169.5–181.5 cM (logarithm of odds LOD = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic
BP), chromosome 2 at 44.1–57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma glucose, and 1.29 for diastolic BP), and chromosome
16 at 45.2–65.4 cM (LOD = 1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that showed suggestive
linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q, 9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C;
and 6q for HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the chromosome 1 region to both MES
and waist circumference ( P genome-wide = 0.002 and 0.019, respectively). In summary, we have found a susceptibility locus on chromosome 1q21-q25 involved in the
pathogenesis of multiple metabolic abnormalities, in particular obesity. Our results confirm the findings of previous studies
on diabetes and related phenotypes. We also suggest the locations of other loci that may contribute to the development of
MES in Hong Kong Chinese.
BP, blood pressure
FCHL, familial combined hyperlipidemia
FPG, fasting plasma glucose
HOMA%IR, insulin resistance index by homeostasis model assessment
ILR, independent linked region
LOD, logarithm of odds
MES, metabolic syndrome
NCEP III, National Cholesterol Education Program Adult Treatment Panel III
QTL, quantitative trait loci
TG, triglyceride
WC, waist circumference
Footnotes
Accepted June 28, 2004.
Received April 27, 2004.
DIABETES
Severe acute respiratory syndrome (SARS) is now a global public health threat with many medical, ethical, social, economic, political, and legal implications. The nonspecific signs and symptoms of ...this disease, coupled with a relatively long incubation period and the initial absence of a reliable diagnostic test, limited the understanding of the magnitude of the outbreak. This paper outlines our experience with public health issues that have arisen during this outbreak of SARS in Hong Kong. We confirmed that case detection, reporting, clear and timely dissemination of information, and strict infection control measures are essential in handling such an infectious disease outbreak. The need for an outbreak response unit is crucial to combat any future outbreak.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type
2 Diabetes
Ying Wang , MD, CHB ,
Maggie C.Y. Ng , BSC, PHD ,
Shao-Chin ...Lee , PHD ,
Wing-Yee So , MBCHB, MRCP ,
Peter C.Y. Tong , MBCHB, MRCP ,
Clive S. Cockram , MD, FRCP ,
Julian A.J.H. Critchley , PHD, FRCP and
Juliana C.N. Chan , MD, FRCP
Divisions of Clinical Pharmacology and Endocrinology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese
University of Hong Kong, Shatin, Hong Kong SAR
Address correspondence and reprint requests to Professor Juliana C.N. Chan, Divisions of Clinical Pharmacology and Endocrinology,
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong
SAR. E-mail: jchan{at}cuhk.edu.hk
Abstract
OBJECTIVE —We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA) n microsatellite and a C/T polymorphism at the 5′ region of the aldose reductase gene ( ALR2 ) in a consecutive cohort of 738 Chinese type 2 diabetic patients.
RESEARCH DESIGN AND METHODS —Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66
had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin
excretion rate (AER) ≥20 μg/min and albumin-to-creatinine ratio ≥3.5 mg/mmol in two urine collections. Retinopathy was defined
by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA) n and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with Bfa I, respectively.
RESULTS —In the whole cohort, patients with diabetic retinopathy ( n = 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy ( n = 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications.
The z+6 carriers of the (CA) n polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy ( n = 551) (4.3 vs. 9.3%, P = 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 ×/÷ 7.2 vs. 21.9 ×/÷ 6.9 μg/min, P = 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with <5 years disease duration. The
group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P = 0.03) and T allele (26.4 vs. 18.5%, P = 0.04) and a lower frequency of the z+6 allele (1.7 vs. 5.5%, P = 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6,
95% CI 1.20–5.83, P = 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19–5.19, P = 0.02) were independent predictors for both diabetic nephropathy and retinopathy.
CONCLUSIONS —Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy
and diabetic retinopathy. Both the z-2 allele of (CA) n polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications.
ACR, albumin-to-creatinine ratio
AER, urinary albumin excretion rate
ALR2, aldose reductase
FPG, fasting plasma glucose
Footnotes
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Accepted April 16, 2003.
Received July 22, 2002.
DIABETES CARE
PDF
