A synthesis of cost-utility analysis literature in infectious disease

The purpose of this review is to understand infectious disease-related cost-utility analyses by describing published analyses, examining growth and quality trends over time, examining factors related to quality, and summarising standardised results. 122 cost-utility analyses and 352 cost-utility ratios were identified. Pharmaceutical interventions were most common (47.5%); three author groups accounted for 42.8% of pharmaceutical ratios. High-volume journals (three or more published cost-utility analyses) published higher quality analyses than low-volume journals (p<0.001). Use of probabilistic sensitivity analysis and discounting at 3% were more frequently found in the years after the US Public Health Service Panel on Cost-Effectiveness in Health and Medicine recommendations (p<0.01). Median ratios varied from US13,500 dollars/quality-adjusted life year (QALY) for immunisations to US810,000 dollars/QALY for blood safety. Publication of infectious disease cost-utility analyses is increasing. The results of cost-utility analyses have important implications for the development of clinical guidelines and resource allocation decisions. More trained investigators and better peer-review processes are needed.     

Maternal HLA class II compatibility in men with systemic lupus erythematosus

OBJECTIVE: Maternal-fetal cell transfer during pregnancy can lead to long-lasting microchimerism, which raises the question of whether microchimerism sometimes contributes to autoimmune disease later in life. In an experimental model, transfusion of parental lymphocytes homozygous for major histocompatibility complex alleles results in systemic lupus erythematosus (SLE). We identified male patients with SLE and healthy male subjects and their mothers in order to investigate the mother-son HLA relationship in SLE risk. Male subjects were selected in order to avoid confounding due to fetal microchimerism, which may occur in women. METHODS: HLA genotyping for DRB1, DQA1, and DQB1 was conducted for sons and their mothers. Thirty men with SLE and their mothers were compared with 76 healthy men and their mothers. RESULTS: Sons with SLE were HLA-identical with their mothers (bidirectionally compatible) for the basic HLA-DRB1 groups encoded by DRB1*01 through DRB1*14 more often than were healthy sons (odds ratio [OR] 5.0, P = 0.006). Each DRB1 group contains multiple allelic variants; male patients with SLE and their mothers often were identical for both DRB1 allelic variants (OR 3.2, P = 0.08). For DQA1 and DQB1, the ORs were 2.3 (P = 0.08) and 2.0 (P = 0.21), respectively. When analysis was limited to male subjects with SLE-associated HLA genes (encoding HLA-DR2 or HLA-DR3), the differences further increased for DRB1 basic groups (OR 7.2, P = 0.01), DRB1 alleles (OR 15.0, P = 0.018), DQA1 6.4 (P = 0.006), and DQB1 (OR 5.7, P = 0.027). No increase in (unidirectional) compatibility of the mother from the son's perspective was observed at any locus. CONCLUSION: We observed increased bidirectional HLA class II compatibility of male SLE patients and their mothers compared with healthy men and their mothers. This observation implies that maternal microchimerism could sometimes be involved in SLE and therefore merits further investigation.     

Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type C disease

A feline model of Niemann–Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.     

Ultrahigh frame rate retrospective ultrasound microimaging and blood flow visualization in mice in vivo

To overcome frame rate limitations in high-frequency ultrasound microimaging, new data acquisition techniques have been implemented for 2-D (B-scan) and color flow visualization. These techniques, referred to as retrospective B-scan imaging (RBI) and retrospective color flow imaging (RCFI) are based on the use of the electrocardiogram (ECG) to trigger signal acquisitions. B-scan and color flow images are reconstructed by retrospectively assembling the processed data on a line-by-line basis. Retrospective techniques are used to produce the first in vivo B-scan and color flow images of mouse carotid arteries at frame rates up to 10,000 fps. Retrospective B-scan images of mouse heart were also produced at frame rates of 1000 fps using a version of RBI implemented on a commercial imaging system (Vevo660, VisualSonics, Toronto, ON, Canada). This technology enables detailed in vivo biomechanical studies of dynamic tissues such as the myocardium of the mouse heart with high temporal resolution.     

Immaturity of IL-18 gene expression and protein production in cord blood (CB) versus peripheral blood (PB) mononuclear cells and differential effects in natural killer (NK) cell development and function

We have previously demonstrated dysregulation of IL-12 and IL-15 gene and protein expression between activated cord blood (CB) versus peripheral blood (PB) mononuclear cells (MNCs). In the present study, we compared IL-18 gene expression and protein production and IL-18 mRNA half-life in basal versus activated CB versus PB MNCs, the effects of IL-18 +/- IL-12 on MNCs IFN-gamma protein production and ex vivo expansion and activation of CB with IL-12 + IL-2 + anti-CD3 +/- IL-18. Basal and activated levels of IL-18 were significantly higher in PB versus CB MNCs (P < 0.05). IL-18 mRNA was coincidental with protein levels and significantly lower in CB (P < 0.05) and its half-life significantly shorter in CB versus PB MNCs (P < 0.05). IL-18 synergistically with IL-12 induced IFN-gamma production from PB greater than CB MNCs (P < 0.05). NK cells expansion (P < 0.001) and cytotoxicity (P < 0.01) was significantly increased with IL-12 + IL-2 + anti-CD3 and IL-18. In summary IL-18 gene expression and protein production are significantly decreased in activated CB versus PB MNCs, in part secondary to increased degradation of CB IL-18 mRNA. These results may have implications for the mechanism(s) in part responsible for the immaturity of CB T-cell immunity.     

Differences in preventive health quality by residency year

BACKGROUND: It is assumed that the performance of more senior residents is superior to that of interns, but this has not been assessed objectively. OBJECTIVE: To determine whether adherence to national guidelines for outpatient preventive health services differs by year of residency training. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred twenty Internal Medicine residents, postgraduate year (PGY)- 1 and PGY -2, attending a University Internal Medicine teaching clinic between June 2000 and May 2003. MEASUREMENTS: We studied 6 preventive health care services offered or received by patients by abstracting data from 1,017 patient records. We examined the differences in performance between PGY-1 and PGY-2 residents. RESULTS: Postgraduate year-2 residents did not statistically outperform PGY-1 residents on any measure. The overall proportion of patients receiving appropriate preventive health services for pneumococcal vaccination, advising tobacco cessation, breast and colon cancer screening, and lipid screening was similar across levels of training. PGY-1s outperformed PGY-2s for tobacco use screening (58%, 51%, P = .03). These results were consistent after accounting for clustering of patients within provider and adjusting for patient age, gender, race and insurance, resident gender, and number of visits during the measurement year. CONCLUSIONS: Overall, patients cared for by PGY-2 residents did not receive more outpatient preventive health services than those cared for by PGY-1 residents. Efforts should be made to ensure quality patient care in the outpatient setting for all levels of training.     

Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks.

BACKGROUND: Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30-90 ms after the shock. OBJECTIVE: The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping. METHODS: In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge needles with six electrodes (2-mm spacing) were spread throughout the remainder of the LV, while 9-12 plunge needles with four electrodes (2-mm spacing) were inserted into the right ventricle. A basket catheter with 32 bipolar recording sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were delivered during 10 episodes of electrically induced ventricular fibrillation. Electrograms of postshock activation cycles were analyzed for Purkinje and myocardial activations. RESULTS: Purkinje activations were recorded before local myocardial activation in 9% of basket electrograms and in 15% of plunge needles during the first postshock activation cycle. Purkinje activations were identified during the first and subsequent several postshock activation cycles in at least one basket and one needle electrogram in 96% and 98% of defibrillation episodes, respectively. CONCLUSIONS: The Purkinje system is active during the early postshock activation cycles after DFT-level shocks. Further studies are required to determine whether activation initiates in the Purkinje system or whether it is activated by the myocardium or by Purkinje-myocardial junctional cells.     

Tricuspid Valve Imaging and Intervention in Pediatric and Adult Patients With Congenital Heart Disease

Tricuspid valve abnormalities in congenital heart disease comprise a wide spectrum, with the most common being Ebstein anomaly and tricuspid valve dysplasia. Tricuspid valve dysfunction may also be secondary to other types of congenital heart disease, including functional tricuspid regurgitation seen in right heart volume overload conditions, such as atrial septal defect and repaired tetralogy of Fallot with severe pulmonary valve regurgitation. Congenitally corrected transposition and Mustard and Senning procedures maintain the right ventricle as the systemic ventricle, and the tricuspid valve is subject to unique hemodynamic stress not typically seen in normal circulation. Surgical treatment of tricuspid valve disease remains the mainstay of therapy; primary catheter-based interventions are uncommon. However, once a tricuspid valve has been replaced with a bioprosthesis, the patient may be a candidate for tricuspid valve-in-valve catheter-based replacement.     

Effects of sodium intake on postural lightheadedness: Results from the DASH‐sodium trial

Lightheadedness after standing contributes to adverse clinical events, including falls. Recommendations for higher sodium intake to treat postural lightheadedness have not been evaluated in a trial setting. The Dietary Approaches to Stop Hypertension (DASH)‐Sodium trial (1998‐1999) tested the effects of the DASH diet and sodium reduction on blood pressure (BP). Participants were randomly assigned to DASH or a typical Western diet (control). During either diet, participants ate three sodium levels (50, 100, 150 meq/d at 2100 kcal) in random order for 30‐days, separated by 5‐day breaks. Participants reported the presence and severity of postural lightheadedness at baseline and after each feeding period. There were 412 participants (mean age 48 years; 57% women; 57% black). Mean baseline SBP/DBP was 135/86 mm Hg; 9.5% reported baseline lightheadedness. Among those consuming the DASH diet, high vs low sodium increased lightheadedness (OR 1.71; 95% CI: 1.01, 2.90; P = 0.047) and severity of lightheadedness (P = 0.02), but did not affect lightheadedness in those consuming the control diet (OR 0.77; 95% CI: 0.46, 1.29; P = 0.32). Among those consuming high vs low sodium in the context of the DASH diet, adults <60 vs ≥60 years old experienced more lightheadedness (P‐interaction = 0.04), along with obese vs non‐obese adults (P‐interaction = 0.01). In the context of the DASH diet, higher sodium intake was associated with more frequent and severe lightheadedness. These findings challenge traditional recommendations to increase sodium intake to prevent lightheadedness.