Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.     

Antiphospholipid antibodies and platelets

The most distinguishing serologic feature of antiphospholipid syndrome (APS) is the moderate to high blood titers of antiphospholipid-binding antibodies (aPL). The pathogenic mechanisms of APS are poorly understood, but may occur as a result of the interaction between anticardiolipin antibodies (aCL), beta-2 glycoprotein-I (β₂GP-I) (the aCL cofactor) and blood platelets. However, the relationship between aCL/β₂GP-I complexes and platelet aggregation has yet to be clearly elucidated. This article will briefly review aPL, β₂GP-I and platelet physiology with respect to recent hypotheses relating aCL/β₂GP-I complexes and platelets.     

An exploration of the concept of directly observed treatment (DOT) for tuberculosis patients: from a uniform to a customised approach.

Tuberculosis (TB) management has moved from chaotic systems and low patient adherence with treatment regimens to the directly observed therapy, short course (DOTS) strategy, which has been described as a new paradigm of TB control. Directly observed treatment (DOT) is only one component of the full DOTS strategy. DOT versus self-administered treatment (SAT) has been the subject of extensive debate, particularly about what approach improves treatment adherence. This debate has been complicated by different case-holding rates and cure outcomes in different contexts where DOT is in place. The increasing range of DOT applications in different settings, including the choice of provider, place, target population, and the extent to which DOT is part of a wider approach, has not been sufficiently taken into account. However, the concrete reality of DOT is an important determinant of the overall success or failure of the programme, and has implications in terms of equity and accessibility of care during treatment. This article aims to go beyond the frequently polarised debate of DOT versus SAT and document the diversity of ways in which DOT has been implemented internationally. We also aim to raise key issues for further discussion, including 1) viewing DOT as part of a complex and lengthy set of interventions that are context-specific, 2) incorporating an equity approach that discusses individual patients' needs and the relationship between the patient and provider, and 3) the role of incentives and enablers. It is anticipated that this exchange of opinion and experiences from different parts of the world will be useful for those involved in the policy formulation and practice of TB management.     

Response to the Valsalva maneuver after the Fontan procedure for tricuspid valve atresia, single ventricle or pulmonic valve atresia

The Valsalva maneuver was performed during cardiac catheterization in 9 patients who had undergone a Fontan operation (Fontan group) and in 10 control subjects. The Fontan group had higher right atrial (RA) pressure (16 +/- 1 vs 4 +/- 0.5 mm Hg, p less than 0.001), lower cardiac index (2.5 +/- 0.1 vs 3.7 +/- 0.2 liters/min/m2, p less than 0.05), lower stroke index (32 +/- 2 vs 44 +/- 2 ml/beat/m2, p less than 0.05), and higher systemic vascular resistance (31 +/- 1 vs 24 +/- 1 units, p less than 0.05) than the control group. Four patients in the Fontan group had a normal 4-phase Valsalva response, and 5 did not (p less than 0.05). RA pressure was similar in those who responded normally and those who did not (16 +/- 0.5 vs 17 +/- 1 mm Hg), whereas in those who responded normally cardiac index was higher (2.9 +/- 0.2 vs 2.2 +/- 0.1 liters/min/m2, p less than 0.05), stroke index was higher (36 +/- 1 vs 28 +/- 1 ml/beat/m2, p less than 0.05), and systemic vascular resistance was lower (28 +/- 1 vs 31 +/- 1, p less than 0.05). It is concluded that cardiac output is a better predictor of a normal response to the Valsalva maneuver than RA pressure in patients after the Fontan procedure. A normal response to the supine Valsalva maneuver suggests a cardiac index greater than 2.4 liters/min/m2 and stroke index greater than 31 ml/beat/m2.     

Empiric use of vancomycin during prolonged treatment-induced granulocytopenia. Randomized, double-blind, placebo-controlled clinical trial in patients with acute leukemia

Because gram-positive infections cause morbidity following intensive antileukemic chemotherapy, the effects of vancomycin versus placebo were evaluated in a randomized, double-blind, placebo-controlled trial in 60 adult patients with acute leukemia and first infectious fever during prolonged (mean of 32 days) granulocytopenia. Gram-positive sepsis was associated with first fever in 17 (28 percent) of the 60 patients. None of 31 patients randomly assigned to receive vancomycin demonstrated gram-positive infection, whereas 16 of 22 patients randomly assigned to receive placebo subsequently had gram-positive infection (seven had sepsis, and nine had local infections; p less than 0.005). All patients with gram-positive infection were then given vancomycin, and all showed prompt clinical responses. The predominant gram-positive organism causing infection was beta-lactam-resistant Staphylococcus epidermis (19 of 44 isolates). Patients randomly assigned to receive vancomycin had more rapid resolution of first infectious fever and fewer total febrile days during the granulocytopenic course than did patients randomly assigned to receive placebo. Although vancomycin had no effect on the presence or absence of documented fungal infection, patients treated with vancomycin received empiric amphotericin B for recurrent or persistent fever later (mean of 14 days after initial antibiotic coverage was begun) than did patients receiving placebo (mean of 9.9 days; p less than 0.005), and thus received fewer total days of empiric amphotericin B therapy (mean of 16.3 days) than did patients given placebo (mean of 24.6 days; p less than 0.01). These data demonstrate that empiric use of vancomycin reduces the morbidity of gram-positive infections following intensive antileukemic therapy and decreases the need for empiric use of toxic amphotericin B.     

Blood Pressure Variations During a Working Day at Age 28: Effects of Different Types of Work and Blood Pressure Level at Age 18

Abstract

During an ordinary work day blood pressure was self-monitored once every hour in two samples of asymptomatic nonmedicating 28-year-old men. They were selected on the basis of previous compulsory blood pressure recordings made at the age of 18 when they had been drafted for military service. Subjects in the ?original hypertensive sample” with ?strain” occupations (hectic and uncontrollable, such as waiter, driver and cook) had more marked elevations of systolic blood pressure during work hours than other subjects.     

Developing a behavioral model for mobile phone-based diabetes interventions

Objectives

Behavioral models for mobile phone-based diabetes interventions are lacking. This study explores the potential mechanisms by which a text message-based diabetes program affected self-management among African-Americans.

Methods

We conducted in-depth, individual interviews among 18 African-American patients with type 2 diabetes who completed a 4-week text message-based diabetes program. Each interview was audio-taped, transcribed verbatim, and imported into Atlas.ti software. Coding was done iteratively. Emergent themes were mapped onto existing behavioral constructs and then used to develop a novel behavioral model for mobile phone-based diabetes self-management programs.

Results

The effects of the text message-based program went beyond automated reminders. The constant, daily communications reduced denial of diabetes and reinforced the importance of self-management (Rosenstock Health Belief Model). Responding positively to questions about self-management increased mastery experience (Bandura Self-Efficacy). Most surprisingly, participants perceived the automated program as a “friend” and “support group” that monitored and supported their self-management behaviors (Barrera Social Support).

Conclusions

A mobile phone-based diabetes program affected self-management through multiple behavioral constructs including health beliefs, self-efficacy, and social support.

Practice implications

Disease management programs that utilize mobile technologies should be designed to leverage existing models of behavior change and can address barriers to self-management associated with health disparities.     

Arginine Vasopressin Immunoreactivity is Decreased in the Hypothalamic Suprachiasmatic Nucleus of Subjects with Suprasellar Tumors

Suprasellar tumors with compression of the optic chiasm are associated with an impaired sleep–wake rhythm. We hypothesized that this reflects a disorder of the biological clock of the human brain, the suprachiasmatic nucleus (SCN), which is located just above the optic chiasm. In order to test this hypothesis, we investigated the expression of two key neuropeptides of the SCN, that is, arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP), as assessed by quantitative immunocytochemistry in post‐mortem hypothalamic tissue of patients with a suprasellar tumor inducing permanent visual field defects. Post‐mortem hypothalamic tissue of 5 patients with a suprasellar tumor inducing permanent visual field defects (acromegaly n = 2, nonfunctioning macro‐adenoma n = 1, macroprolactinoma n = 1, infundibular metastasis of a colorectal adenocarcinoma n = 1) and 15 age‐ and gender‐matched controls was obtained from the Netherlands Brain Bank. Total AVP immunoreactivity in the SCN was lower in patients with a suprasellar tumor than in controls (P = 0.03). By contrast, total VIP immunoreactivity was not different between patients and controls (P = 0.44). Suprasellar tumors leading to permanent visual field defects are associated with reduced AVP, but not VIP immunoreactivity, in the SCN. These findings raise the possibility that selective impairment of the SCN contributes to sleep–wake disturbances in these patients.