Cost-effectiveness of immunizations: The Gambia revisited

This paper reports on the results of an intensive study of thecosts and cost-effectiveness of the Expanded Programme on Immunization(EPI) in The Gambia. Costs in 1988, for the nation as a wholeand for a large sample of specific local delivery sites, andtheir relation to vaccination coverage are presented. The total and average costs of the full national EPI fell impressivelyin The Gambia from about US$1.50 per dose in the early 1980sto US$0.60 in 1988. That conclusion is reinforced by improvementsin vaccination coverage and by a very large decline in costper fully immunized child from about US$19.00 to US$5.64. Comparisonsof the latter finding with the earlier Gambian value, and withother developing countries' figures, suggest a highly cost-effectiveEPI for 1988. Some of the major reasons for this were good administration,widespread deployment of delivery teams, and effective socialmobilization (community awareness) efforts. The study offers site-specific cost estimates that reveal largevariations in average costs among centres. Lower average costsappear to be based on economies of scale and greater intensityof use of facilities and teams, together with better management.As with the estimates for the full national programme, thesevariations are not explicable simply as artefacts of methodologicaltechniques and assumptions. Although recent (1988) Gambian data indicate relatively lowcosts and high cost-effectiveness, the continuation of, andprobable increase in, other threats to health than vaccine-preventablediseases pose daunting challenges to all parties concerned withimproving the allocation of scarce resources for the wellbeingof the Gambian people, and of others in the developing world.     

Pentoxifylline improves haemoglobin and interleukin‐6 levels in chronic kidney disease

Aim: To assess whether pentoxifylline improves anaemia of chronic kidney disease (CKD) via suppression of interleukin‐6 (IL‐6) and improved iron mobilization. Background: CKD patients may have elevated IL‐6 and tumour necrosis factor alpha levels. These cytokines can increase hepcidin production, which in turn reduces iron release from macrophages resulting in reduced availability of iron for erythropoiesis. In experimental models, pentoxifylline was shown to reduce IL‐6 expression. Methods: We studied 14 patients with stages 4–5 CKD (glomerular filtration rate <30mL/min per 1.73 m²) due to non‐inflammatory renal diseases. None of the patients had received immunosuppressive or erythropoietin‐stimulating agents or parenteral iron. Patients had weekly blood tests for iron studies and cytokines during a control run‐in period of 3 weeks and during 4 weeks of pentoxifylline treatment. Results: Ten patients (eGFR 23 ± 6 mL/min) completed the study. At the end of the run‐in period average haemoglobin was 111 ± 5 g/L, ferritin 92 ± 26 µg/L, transferrin saturation 15 ± 3% and circulating IL‐6 10.6 ± 3.8 pg/mL. Tumour necrosis factor alpha values were below threshold for detection. Treatment with pentoxifylline reduced circulating IL‐6 (6.6 ± 1.6 pg/mL, P < 0.01), increased transferrin saturation (20 ± 5%, P < 0.003) and decreased serum ferritin (81 ± 25 µg/L, P = NS). Haemoglobin increased after the second week of pentoxifylline, reaching 123 ± 6 g/L by week 4 (P < 0.001). Conclusions: Pentoxifylline reduces circulating IL‐6 and improves haemoglobin in non‐inflammatory moderate to severe CKD. These changes are associated with changes in circulating transferrin saturation and ferritin, suggesting improved iron release. It is hypothesized that pentoxifylline improves iron disposition possibly through modulation of hepcidin.     

Update on Dedicated Bifurcation Stents

Coronary bifurcation lesions represent an area of ongoing challenge in interventional cardiology. Contemporary studies using drug-eluting stents report a reduction in main vessel (MV) restenosis; however, residual stenosis and restenosis at side-branch ostium remain an issue. Multiple two-stent bifurcation strategies exist, including T-stenting, V-stenting, simultaneous kissing stenting, culotte stenting, and crush stenting technique. Each strategy has its own advantages and disadvantages, but on the basis of results of numerous randomized trials, the provisional approach of implanting one stent on the main branch has became the default approach to most bifurcation lesions. Dedicated bifurcation stents have been designed to specifically address some of the shortcomings of the conventional percutaneous approach to bifurcation intervention. The majority of the devices are aimed at facilitating the provisional approach. Dedicated bifurcation stents should enable all operators to treat the side-branch ostium simultaneously with the main branch, preserving a safe, permanent access to side branch during the procedure. In the future, the use of these new devices will probably enhance the interaction between adequate mechanical scaffolding and accurate delivery of the appropriate dosage of any new antirestenosis drugs. There are currently 11 devices available that either have completed or are undergoing first-in-man trials. The development of further drug-eluting platforms and larger controlled studies should demonstrate their clinical applicability, efficacy, and safety before they are widely incorporated into daily practice.     

Embolic Implications of Combined Risk Factors in Patients with Patent Foramen Ovale (the CARPE Criteria): Consideration for Primary Prevention Closure?

Background: Large patent foramen ovale (PFO), spontaneous right‐to‐left shunt, large atrial septal aneurysm (ASA), coagulation abnormalities, and prominent eustachian valve (EV) have all been independently suggested as risk factors for recurrent stroke. We sought to retrospectively evaluate risk of stroke and impact of transcatheter PFO closure in patients with concurrent large PFO, spontaneous right‐to‐left shunt, large ASA, coagulation abnormalities, and prominent EV. Methods: Between March 2006 and October 2008, 36 (mean age 44 ± 10.9 years, 28 females) out of 120 consecutive patients referred to our center for transcatheter PFO closure had concomitant diagnosis of (a) large PFO on transcranial Doppler (TCD) and transesophageal echocardiography (TEE), (b) spontaneous right‐to‐left shunt on TCD, (c) large ASA, (d) prominent EV, and (e) coagulation abnormalities. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative TEE and brain magnetic resonance imaging (MRI), with subsequent intracardiac echocardiographic‐guided transcatheter PFO closure. Results: Compared to the remaining PFO population in the same period, patients with all five concomitant features had more ischemic brain lesions on MRI, previous history of recurrent stroke, more frequently a history of venous thromboembolism, and more severe migraine with aura. The concomitance of all the features confers the highest risk of recurrent stroke (OR 9.9, 3.0–18 [95% CI], P < 0.001). Conclusions: Despite its small sample size and nonrandomized retrospective nature, this is the first study to suggest that patients with concurrence of all the investigated characteristics have potentially a higher risk of stroke compared to controls. We thus propose the CARP criteria as a basis for further larger, longitudinal studies to assess the potential benefits of transcatheter closure in this patient subset in the absence of clinical recurrent stroke.     

CELL INFILTRATEN PROGRESSIVE PIGMENTED PURPURA (SCHAMBERG'S DISEASE): IMMUNOPHENOTYPE, ADHESION RECEPTORS, AND INTERCELLULAR RELATIONSHIPS

Background. Progressive pigmented purpura (Schamberg's disease), a form of purpura pigmentosa chronica, is a lymphocytic capillaritis of unknown etiology and obscure pathogenesis. Our purpose was to assess the expression of cell membrane antigens (CD3, CD4, CD1a, CD36), of adhesion receptors (leukocyte function adhesion 1, LFA-1, endothelial leukocyte adhesion molecule 1, ELAM-1) intercellular adhesion molecule 1, ICAM-1), and the intercellular relationships in the early phase of the disease. Methods. Quantitative immunohistochemistry and electron-microscopy were performed on specimens of five subjects, aged 45 to 63 years. These studies were repeated in two patients after treatment with topical corticosteroid (betamethasone valerate cream 0.1%) and psoralen-ultraviolet A (puva). Results. The infiltrate consisted mainly of CD4+ lymphocytes and CD1a+ dendritic cells. Electron-microscopic investigation showed typical lymphocytes and two distinct types of dendritic cells. In the very early phase of the disease the adhesion receptors LFA-i and ICAM-1 were expressed intensely by all infiltrating cells; the adhesion receptors icam-1 and ELAM-i were expressed by endothelial cells. Close contact occured between lymphocytes and dendritic cells. After PUVA (120 J per cm²) and topical steroid therapy the infiltrate disappeared completely. Conclusions. These data suggest that a cell-mediated immune mechanism may be important in progressive pigmented purpura and that the early endothelial expression     

SERUM EOSINOPHIL CATIONIC PROTEIN (ecp) IN BULLOUS PEMPHIGOID

Background. The importance of eosinophils in the pathogenesis of the major forms of pemphigoid (bullous pemphigoid, cicatricial pemphigoid, herpes gestationis) remains to be confirmed. Methods. To evaluate the role of eosinophilic Infiltrates in these diseases and to detect the presence and activity of eosinophils, we compared the serum levels of eosinophil cationic protein (ecp ), an eosinophil-derived protein, in 11 healthy subjects and in 10 patients with pemphigoid diseases (8 with bullous pemphigoid, one with cicatricial pemphigoid, and one with herpes gestationis). The serum of two patients with epidermolysis bullosa acquisita (l EBA) and one with linear IgA bullous dermatosis (labd ) were utilized as a further control. Results. There was a significant difference between the mean of serum ecp levels in patients with pemphigoid diseases (25.1 ± 12.3 μg/L, M = SD) and control subjects (2.30 ± 2.41, μg/L ± SD 2.41) (T = 4.272 P < 0.0001). The two patients with EBA (10.8 and 17.7 μg/L) showed contrasting results; the patient with labd had normal ecp serum levels. The serum levels of ecp were not significantly correlated with the blood eosinophil count (R = 0.103; P = 0.777) in any of the cases. Conclusions. In pemphigoid disease, the serum levels of ecp seem to be correlated with the activated secreting and tissue-damaging eosinophils found in the dermis, supporting the concept of an active participation of eosinophils in generating cutaneous lesions.