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Purpose Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. Methods This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. Results Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor ( n  = 21, 8%) and non-poor ( n  = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4–34.8) and 5.4 (95% CI 4.1–7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7–7.0, p  < 0.01). Conclusion Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. Trial registry POET ClinicalTrials.gov number, NCT01375257.

In this randomized, controlled trial conducted at Danish cardiac centers, intravenous antibiotic therapy was compared with partial oral antibiotic therapy for the treatment of bacterial endocarditis. The outcomes were similar in the two groups.

The 5-year outcomes from the Partial Oral Treatment of Endocarditis (POET) trial show continued effectiveness of oral antibiotic therapy as compared with intravenous antibiotic therapy for endocarditis.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

This letter describes outcomes of the POET trial at a median follow-up of 3.5 years. The authors found that in patients with endocarditis on the left side of the heart, a change from intravenous antibiotic treatment to early oral antibiotic treatment was not associated with delayed treatment failure.

Measurement of serum insulin-like growth factor I (IGF-I) concentrations remains the single most important tool in the evaluation of growth hormone (GH) replacement in GH-deficient adults, and the therapeutic goal is to maintain the level within the age-adjusted normal range. In healthy adults, IGF-I levels do not differ between males and females, whereas spontaneous GH secretion is approximately twofold higher in females. Untreated GH-deficient women exhibit lower IGF-I levels compared with men, and the increase in serum IGF-I during GH replacement is also significantly less. Put together, these data suggest resistance to GH in women, which in healthy individuals is compensated for by increased GH secretion. Administration of oral oestrogen in healthy post-menopausal women suppresses hepatic IGF-I production and increases pituitary GH release, and oral oestrogen replacement in women with GH deficiency lowers IGF-I concentrations and increases the amount of GH necessary to obtain IGF-I target levels during treatment. These data clearly suggest that hepatic suppression of IGF-I production by oestrogen subserves the gender difference in GH sensitivity, but it is also likely that sex steroids may interact with the GH/IGF axis at further levels. There is also circumstantial evidence to indicate that testosterone stimulates IGF-I production, and it is speculated that a certain threshold level of androgens is essential to ensure hepatic IGF-I production. Whether these data should translate into earlier discontinuation of oestrogen replacement therapy in adult women with hypopituitarism merits consideration.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared to continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis (IE). We aimed to analyze whether step-down oral therapy compared to continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients undergoing surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy and the primary endpoint (composite of all-cause mortality, unplanned cardiac surgery, embolic event or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68±12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared to patients with small vegetations (n=244) (65% vs 20%, p<0.001). During a median 1406 days of follow-up, 146 patients reached the primary endpoint. Large vegetations were not associated with the primary endpoint (HR 0.74 [95% CI 0.47-1.18], p=0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy safe in the presence of a large vegetation at diagnosis and among patients undergoing early cardiac surgery.

In order to provide an estimation of the direct and indirect benefits of pneumococcal vaccination with three protein-conjugate pneumococcal vaccines (PCV) we described the epidemiology and mortality from invasive pneumococcal disease (IPD) in Denmark between 2000 and 2005. Approximately 1080 cases were registered annually during the period. The overall incidence of IPD increased significantly, from 15.4 cases per 100,000 population in 2000 to 20.7 cases per 100,000 in 2005 ( p < 0.01), mainly due to an increase in bacteraemia cases. The serotype coverage in children under 5 years varied from 64% to 91% depending on the PCV used. The mean mortality proportion after IPD was 18%, with approximately 190 deaths annually. One to two deaths among children younger than 5 years and approximately 50 deaths related to IPD caused by vaccine serotypes among older age groups could be prevented annually by introducing a PCV. Approximately 70% of all deaths occurred in adults over 65 years, underlining the need for protection against IPD in this age group.

Growth hormone (GH) replacement is a prolonged and expensive treatment modality which involves daily subcutaneous injections in children and adults. Efforts have been made, therefore, to develop short-term tests to predict long-term clinical response. The so-called insulin-like growth factor I (IGF-I) generation test was originally introduced in order to select responders to GH among short children without classical GH deficiency. A positive correlation between short-term increase in serum IGF-I and linear growth has, however, only been reported in a minority of studies. There is no single outcome measure available in GH-deficient adults, and no evidence of a correlation between IGF-I and the effects of GH replacement on factors such as body composition or physical fitness. In conclusion, no reliable short-term test to predict long-term response to GH replacement is available in either children or adults. For safety reasons, however, measurement of serum IGF-I concentrations in GH-deficient patients remains an important means of monitoring during GH replacement.

Two questions motivated this study: 1) Will meteorological droughts become more frequent and severe during the twenty-first century? 2) Given the projected global temperature rise, to what extent does the inclusion of temperature (in addition to precipitation) in drought indicators play a role in future meteorological droughts? To answer, we analyzed the changes in drought frequency, severity, and historically undocumented extreme droughts over 1981–2100, using the standardized precipitation index (SPI; including precipitation only) and standardized precipitation-evapotranspiration index (SPEI; indirectly including temperature), and under two representative concentration pathways (RCP4.5 and RCP8.5). As input data, we employed 103 high-resolution (0.44°) simulations from the Coordinated Regional Climate Downscaling Experiment (CORDEX), based on a combination of 16 global circulation models (GCMs) and 20 regional circulation models (RCMs). This is the first study on global drought projections including RCMs based on such a large ensemble of RCMs. Based on precipitation only, ∼15% of the global land is likely to experience more frequent and severe droughts during 2071–2100 versus 1981–2010 for both scenarios. This increase is larger (∼47% under RCP4.5, ∼49% under RCP8.5) when precipitation and temperature are used. Both SPI and SPEI project more frequent and severe droughts, especially under RCP8.5, over southern South America, the Mediterranean region, southern Africa, southeastern China, Japan, and southern Australia. A decrease in drought is projected for high latitudes in Northern Hemisphere and Southeast Asia. If temperature is included, drought characteristics are projected to increase over North America, Amazonia, central Europe and Asia, the Horn of Africa, India, and central Australia; if only precipitation is considered, they are found to decrease over those areas.