Paper electrocardiograph strips may contain overlooked clinical information in screen-detected type 2 diabetes patients.

BACKGROUND: A large number of nondigitized electrocardiograph (ECG) strips are routinely collected in larger cohort studies such as the ADDITION study (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care). These ECG strips are routinely read manually but may contain overlooked information revealing cardiac autonomic dysfunction. The aim of this study was to investigate whether clinical information may be lost using manual R wave to R wave (RR) interval measurements in the calculation of heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). METHOD: From the Danish part of the ADDITION study, we randomly selected 120 T2DM patients at baseline of the ADDITION study. Analysis of the ECG strips was performed using two different methods: (1) by experienced technicians using rulers and (2) by experienced technicians using a high-resolution computer-assisted method. Calculation of heart rate and time domain HRV [standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive differences (RMSSD)] were performed with the same software. RESULTS: When comparing results from the two methods, the following values of Pearson's r are obtained: 0.98 for heart rate, 0.76 for SDNN, and 0.68 for RMSSD. These results indicate that heart rate and HRV measurements by the computer-assisted and manually based methods correlate. However, Bland-Altman plots and Pitman's test of difference in variance revealed poor agreements (p < .01) for both HRV measurements (SDNN and RMSSD); only heart rate showed substantiated agreement (p = .54) between the two methods. Low HRV was statistically significantly associated to high heart rate, systolic blood pressure, and diastolic blood pressure in these screen-detected T2DM patients. CONCLUSIONS: Paper ECG strips may contain overlooked clinical information on the status of autonomic function in patients with T2DM. In our study, manual measurements of RR intervals were inferior to the computer-assisted method. Based on this study, we recommend cautiousness in the clinical use and interpretation of HRV based on manual or low resolution measurements of RR intervals from ECG strips. High resolution measurements of RR intervals reveal significant associations between low HRV and high heart rate, systolic blood pressure, and diastolic blood pressure among patients with screen-detected T2DM. It is feasible to use a computer-assisted method to determine RR intervals in patients with T2DM.

Burden of illness of the 2009 pandemic of influenza A (H1N1) in Denmark.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5-14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5-5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.

Intra- and extracellular activity of linezolid against Staphylococcus aureus in vivo and in vitro.

BACKGROUND AND AIMS: Treatment of Staphylococcus aureus infections remains problematic (slow responses and frequent recurrences). Intracellular persistence of the S. aureus could explain those difficulties because of impaired intracellular efficacy of antibiotics. Our aim was to study linezolid for its intracellular activity. METHODS: (i) Pharmacodynamic (PD) analysis of intracellular activity using in vitro (THP-1 macrophages) and in vivo (mouse peritonitis) models with determination of key dose-response parameters [maximal relative efficacy (E(max)), relative potency (EC(50)) and static concentration (C(static))] towards methicillin-susceptible S. aureus (ATCC 25923; clinical isolate) with linezolid MICs of 4 mg/L; (ii) pharmacokinetic (PK) analysis in uninfected mice for determination of C(max), AUC and half-life for total and free drug; and (iii) determination of the predictive PK/PD parameter (fT > MIC, fAUC(24)/MIC or fC(max)/MIC) for therapeutic outcome. RESULTS: In vitro, linezolid showed an E(max) of approximately 1 log(10) cfu reduction compared with initial inoculum both intra- and extracellularly and an approximately 3-fold increased relative potency (lower EC(50) and C(static)) intracellularly. In vivo, the efficacy of linezolid was impaired (<0.5 log(10) reduction extracellularly; failure to reduce the cfu to less than the initial load intracellularly) with, however, an increased intracellular potency (lower EC(50)). Infection outcome correlated better with the fAUC(24)/MIC (R(2) = 55%) than with the fT > MIC parameter (R(2) = 51%) for the extracellular compartment, but no parameter emerged as significant for the intracellular compartment. CONCLUSIONS: Linezolid exerts only a weak intracellular activity against the strains of S. aureus tested, even though, in contrast to most other antibiotics, its potency does not appear impaired in comparison with the extracellular activity.

Intra- and extracellular activities of dicloxacillin against Staphylococcus aureus in vivo and in vitro.

Antibiotic treatment of Staphylococcus aureus infections is often problematic due to the slow response and recurrences. The intracellular persistence of the staphylococci offers a plausible explanation for the treatment difficulties because of the impaired intracellular efficacies of the antibiotics. The intra- and extracellular time- and concentration-kill relationships were examined in vitro with THP-1 cells and in vivo by use of a mouse peritonitis model. The in vivo model was further used to estimate the most predictive pharmacokinetic/pharmacodynamic (PK/PD) indices (the ratio of the maximum concentration of drug in plasma/MIC, the ratio of the area under the concentration-time curve/MIC, or the cumulative percentage of a 24-h period that the free [f] drug concentration exceeded the MIC under steady-state pharmacokinetic conditions [fT(MIC)]) for dicloxacillin (DCX) intra- and extracellularly. In general, DCX was found to have similar intracellular activities, regardless of the model used. Both models showed (i) the relative maximal efficacy (1-log-unit reduction in the numbers of CFU) of DCX intracellularly and (ii) the equal relative potency of DCX intra- and extracellularly, with the MIC being a good indicator of the overall response in both situations. Discordant results, based on data obtained different times after dosing, were obtained from the two models when the extracellular activity of DCX was measured, in which the in vitro model showed a considerable reduction in the number of CFU from that in the original inoculum (3-log-unit decrease in the number of CFU after 24 h), whereas the extracellular CFU reduction achieved in vivo after 4 h did not exceed 1 log unit. Multiple dosing of DCX in vivo revealed increased extra- and intracellular efficacies (2.5 log and 2 log units of reduction in the numbers of CFU after 24 h, respectively), confirming that DCX is a highly active antistaphylococcal antibiotic. PK/PD analysis revealed that fT(MIC) is the index that is the most predictive of the outcome of infection both intra- and extracellularly.