In patients with severe sepsis, albumin replacement in addition to crystalloid administration conferred no benefit, as compared with crystalloids alone, with respect to mortality at 28 or 90 days. ...Post hoc analysis suggested a possible benefit in patients with septic shock.
For decades, human albumin has been administered to patients to provide adequate oncotic pressure and intravascular volume.
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In 1998, however, a report from the Cochrane Injuries Group Albumin Reviewers indicated that the administration of albumin may be potentially harmful in critically ill patients, as compared with the administration of crystalloid solutions.
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Subsequent meta-analyses reported contradictory findings.
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,
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To clarify this issue, a large, double-blind, randomized trial (the Saline versus Albumin Fluid Evaluation SAFE study)
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was conducted, in which 4% albumin solution was compared with normal saline as fluid replacement in critically ill patients, with results indicating that albumin administration was . . .
Based on a synthetic overview that embraces the evolution of the ‘health’ concept, and its related institutions, from the role of health as
the main indicator of fundamental human rights
—as ...envisaged in the Universal Declaration of Human Rights—to its qualification as
the systems of disease control dependent on criteria of economic sustainability
, the paper focuses on the implications and the impact of such evolution in two model scenarios which are centred on the COVID-19 pandemia. The article analyses COVID-19 both in the characteristics of its global dynamics and in its concrete management, as performed in a model medium income country, Argentina. In a world which has progressively assigned market values and goods an absolute strategic and political priority over the health needs and the rights to health of individual and peoples, the recognition of health as human right is confined to aspirational recommendations and rather hollowed out declarations of good will.
Summary Background Daily aspirin reduces the long-term risk of death due to cancer. However, the short-term effect is less certain, especially in women, effects on cancer incidence are largely ...unknown, and the time course of risk and benefit in primary prevention is unclear. We studied cancer deaths in all trials of daily aspirin versus control and the time course of effects of low-dose aspirin on cancer incidence and other outcomes in trials in primary prevention. Methods We studied individual patient data from randomised trials of daily aspirin versus no aspirin in prevention of vascular events. Death due to cancer, all non-vascular death, vascular death, and all deaths were assessed in all eligible trials. In trials of low-dose aspirin in primary prevention, we also established the time course of effects on incident cancer, major vascular events, and major extracranial bleeds, with stratification by age, sex, and smoking status. Results Allocation to aspirin reduced cancer deaths (562 vs 664 deaths; odds ratio OR 0·85, 95% CI 0·76–0·96, p=0·008; 34 trials, 69 224 participants), particularly from 5 years onwards (92 vs 145; OR 0·63, 95% CI 0·49–0·82, p=0·0005), resulting in fewer non-vascular deaths overall (1021 vs 1173; OR 0·88, 95% CI 0·78–0·96, p=0·003; 51 trials, 77 549 participants). In trials in primary prevention, the reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In six trials of daily low-dose aspirin in primary prevention (35 535 participants), aspirin reduced cancer incidence from 3 years onwards (324 vs 421 cases; OR 0·76, 95% CI 0·66–0·88, p=0·0003) in women (132 vs 176; OR 0·75, 95% CI 0·59–0·94, p=0·01) and in men (192 vs 245; OR 0·77, 95% CI 0·63–0·93, p=0·008). The reduced risk of major vascular events on aspirin was initially offset by an increased risk of major bleeding, but effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction 3·13 95% CI 1·44–4·82 per 1000 patients per year) from 3 years onwards. Case-fatality from major extracranial bleeds was also lower on aspirin than on control (8/203 vs 15/132; OR 0·32, 95% CI 0·12–0·83, p=0·009). Interpretation Alongside the previously reported reduction by aspirin of the long-term risk of cancer death, the short-term reductions in cancer incidence and mortality and the decrease in risk of major extracranial bleeds with extended use, and their low case-fatality, add to the case for daily aspirin in prevention of cancer. Funding None.
Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide in Val-HeFT (Valsartan Heart Failure Trial) Serge Masson, Roberto Latini, Inder S. Anand, Simona Barlera, Laura Angelici, ...Tarcisio Vago, Gianni Tognoni, Jay N. Cohn, for the Val-HeFT Investigators We assessed the prognostic value of repeated determinations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in a large population of patients with stable and chronic heart failure (HF). A single determination of NT-proBNP showed a higher prognostic discrimination during the course of a strict clinical monitoring period than continuous changes of concentrations. Categorical changes across a threshold value predicted outcome independently of a single determination. Serial determinations of NT-proBNP and classification into few categories of changes may be a superior strategy for risk stratification of patients with chronic and stable HF, and may offer an aid in monitoring these patients.
The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II ...weak opioids or low-dose step III strong opioids.
In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine. The primary outcome was the number of responder patients, defined as patients with a 20% reduction in pain intensity on the numerical rating scale.
A total of 240 patients with cancer (118 in the low-dose morphine and 122 in the weak-opioid group) were included in the study. The primary outcome occurred in 88.2% of the low-dose morphine and in 57.7% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P < .001). The percentage of responder patients was higher in the low-dose morphine group, as early as at 1 week. Clinically meaningful (≥ 30%) and highly meaningful (≥ 50%) pain reduction from baseline was significantly higher in the low-dose morphine group (P < .001). A change in the assigned treatment occurred more frequently in the weak-opioid group, because of inadequate analgesia. The general condition of patients, which was based on the Edmonton Symptom Assessment System overall symptom score, was better in the morphine group. Adverse effects were similar in both groups.
In patients with cancer and moderate pain, low-dose morphine reduced pain intensity significantly compared with weak opioids, with a similarly good tolerability and an earlier effect.
Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We ...evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).
This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.
Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).
In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.
The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far ...produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low‐dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow‐up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To assure comparability, we conducted a propensity score matching analysis. The two groups (PHL n = 342 and HU n = 681) were well balanced for the parameters included in the propensity score (overall balance: χ2 = 2.44, P = 0.964). Over a comparable period of follow‐up (PHL = 29.9 vs. HU = 34.7 months), we documented an advantage of HU over PHL consistently significant with respect to the incidence of fatal/non‐fatal cardiovascular (CV) events (5.8 vs. 3.0 per 100 person‐years in PHL vs. HU group, P = 0.002) and myelofibrosis transformation that was only experienced by patients of PHL group. Evolution to acute leukemia was registered in three patients (two in PHL and one in HU group). The excess of mortality and total CV events in the PHL patients was restricted to the high‐risk group, and, compared with HU cases, was significant higher in the PHL patients who failed to reach the hematocrit target < 0.45% (P = 0.000). In conclusion, this analysis provides reliable and qualified estimates of the therapeutic profile of HU and PHL treatments for future experimental studies and for the management of PV in clinical practice.
Angiotensin II may contribute to the progression of heart failure. In this trial, valsartan, an angiotensin-receptor blocker, reduced the need for hospitalization for heart failure but had no effect ...on overall mortality. According to a post hoc analysis, patients treated with valsartan who were also receiving both an angiotensin-converting–enzyme (ACE) inhibitor and a beta-blocker had increased mortality; patients receiving one or neither of these types of drugs had reduced mortality.
Pharmacotherapy for heart failure has advanced considerably in recent years as clinical trials have demonstrated favorable long-term effects of angiotensin-converting–enzyme (ACE) inhibitors
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–
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and beta-blockers
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–
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on morbidity and mortality. Despite the use of these potent drugs, heart failure remains the leading reason for hospitalization in the Medicare population,
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mortality among patients with heart failure is high, and the quality of life is low.
Angiotensin II, a potent vasoconstrictor and growth-stimulating hormone, may contribute to the impairment of left ventricular function and the progression of heart failure through increased impedance of left ventricular emptying,
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adverse long-term structural effects on the . . .
Summary Background Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of ...published and unpublished data whether any relation exists between statin use and development of diabetes. Methods We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I2 statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis. Findings We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio OR 1·09; 95% CI 1·02–1·17), with little heterogeneity ( I2 =11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150–852) patients with statins for 4 years resulted in one extra case of diabetes. Interpretation Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change. Funding None.
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