Population Pharmacokinetics of Flucloxacillin In Bone and Soft Tissue– Standard Dosing is Not Sufficient to Achieve Therapeutic Concentrations

Pharmaceutical Research - Flucloxacillin is a β-lactam penicillin commonly used in the treatment of bone and soft tissue infections. In a recent porcine study, we found surprisingly low time...     

Telecardiología: pasado,presente y futuro

Technological advances over the past decades have allowed improved diagnosis and monitoring of patients with acute coronary syndromes as well as patients with advanced heart failure. High-quality digital recordings transmitted wirelessly by cellular telephone networks have augmented the prehospital use of transportable electrocardiogram machines as well as implantable devices for arrhythmia monitoring and therapy. The impact of prehospital electrocardiogram recording and interpretation in patients suspected of acute myocardial infarction should not be underestimated. It enables a more widespread access to rapid reperfusion therapy, thereby reducing treatment delay, morbidity and mortality. Further, continuous electrocardiogram monitoring has improved arrhythmia diagnosis and dynamic ST-segment changes have been shown to provide important prognostic information in patients with acute ST-elevation myocardial infarction. Likewise, remote recording or monitoring of arrhythmias and vital signs seem to improve outcome and reduce the necessity of re-admissions or outpatient contacts in patients with heart failure or arrhythmias. In the future telemonitoring and diagnosis is expected to further impact the way we practice cardiology and provide better care for the patient with cardiovascular disease.     

Significance of T-wave amplitude and dynamics at the time of reperfusion in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background

Peri-interventional T-wave changes may reflect the microvascular reperfusion status and potentially carry early independent, prognostic information in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI).

Methods

The first available electrocardiogram (ECG) (index ECG) and the ECG recorded immediately post-PCI were analyzed for T-wave morphology in 207 patients with STEMI. Absolute T-wave amplitude was recorded and any change in T-wave amplitude from index ECG to post-PCI ECG was calculated. Continuous ST monitoring was performed from hospital arrival until 90 minutes after PCI. Maximum troponin level and left ventricular ejection fraction were evaluated before discharge. Final infarct size was assessed by myocardial perfusion imaging after 1 month.

Results

Large, positive T-wave amplitude in the index ECG and the post-PCI ECG was associated with delayed ST resolution after PCI. In the post-PCI ECG, T-wave amplitude was positively associated with troponin-T value (P < .001) and final infarct size (P = .036), and inversely associated with left ventricular ejection fraction (P < .001). However, T-wave amplitude in the post-PCI ECG was also associated with procedural increase in ST elevation (P < .001) and inversely associated with spontaneous ST resolution (P < .017). A net decrease in T-wave amplitude during reperfusion therapy was associated with faster microvascular reperfusion as evaluated by time to ST resolution.

Conclusion

Large T-wave amplitudes in static pre- and post-PCI ECGs are associated with delayed microvascular reperfusion, whereas the dynamic development of more negative T waves during PCI is associated with earlier microvascular reperfusion. However, in the acute setting, T waves provide little incremental information when compared to ST parameters available in the per-interventional phase.     

Clinical Inertia in People With Type 2 Diabetes: A retrospective cohort study of more than 80,000 people

OBJECTIVE

To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control.

RESEARCH DESIGN AND METHODS

This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011.

RESULTS

In people with HbA_1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA_1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA_1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1–43.6% and with insulin 5.1–12.0%.

CONCLUSIONS

There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.Type 2 diabetes is a progressive disease that often requires stepwise intensification of treatment to maintain good glycemic control (1). It is also well established that timely treatment of people with type 2 diabetes has a beneficial effect on outcomes, so tight glycemic control is advocated to reduce the risk of development or progression of micro- or macrovascular complications (2,3). The recent American Diabetes Association guidelines recommend starting metformin alongside lifestyle modifications at diagnosis, aiming for an HbA_1c target of <7% (<53 mmol/mol) (4). The joint American Diabetes Association/European Association for the Study of Diabetes Position Statement also endorses HbA_1c <7% (<53 mmol/mol) for most people with diabetes but recommends individualized targets (5). Finally, the guidelines from the National Institute for Health and Care Excellence (NICE) in the U.K., most recently updated in 2009, recommend lifestyle measures as the first step in the clinical treatment algorithm. If HbA_1c is then ≥6.5% (≥48 mmol/mol), metformin is recommended as the first-line oral antidiabetes drug (OAD) prescribed (6,7). Additional OADs may be added if glycemic control continues to remain above the recommended target of 6.5% (48 mmol/mol), and if HbA_1c is ≥7.5% (≥ 58 mmol/mol) while the patient is already receiving at least two OADs, further intensification of treatment, including the use of insulin, is recommended (6,7).Despite good-quality evidence of tight glycemic control, particularly early in the disease trajectory (3), people with type 2 diabetes often do not reach recommended glycemic targets. Baseline characteristics in observational studies indicate that both insulin-experienced and insulin-naïve people may have mean HbA_1c above the recommended target levels, reflecting the existence of patients with poor glycemic control in routine clinical care (8–10). In a prospective, population-based study using retrospective observational data, it was reported that at insulin initiation people had experienced a high glycemic burden for 5 years with HbA_1c >8% (>64 mmol/mol) and for 10 years with HbA_1c >7% (>53 mmol/mol) (11). U.K. data, based on an analysis reflecting previous NICE guidelines, show that it takes a mean of 7.7 years to initiate insulin after the start of the last OAD (in people taking two or more OADs) and that mean HbA_1c is ~10% (86 mmol/mol) at the time of insulin initiation (12). This is also reflected in poor HbA_1c levels even after intensification of treatment. This failure to intensify treatment in a timely manner has been termed clinical inertia; however, data are lacking on clinical inertia in the diabetes-management pathway in a real-world primary care setting, and studies that have been carried out are, relatively speaking, small in scale (13,14). This retrospective cohort analysis investigates time to intensification of treatment in people with type 2 diabetes treated with OADs and the associated levels of glycemic control, and compares these findings with recommended treatment guidelines for diabetes.