Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis

BACKGROUND: Mortality caused by tetanus is still a serious health problem in developing countries. Apart from immunization, early treatment with equine antitetanus serum (ATS) or human tetanus immunoglobulin (TIG) is the real treatment that can avoid death. On pathophysiological grounds intrathecal administration would be preferred because of high concentrations of the antiserum in cerebrospinal fluid and thus around the nerve roots. Many studies concluded on its effectiveness whereas others did not find any superiority of this method. However, most of those studies were not random and/or had no sufficient weight. OBJECTIVE: To assess the efficacy of intrathecal therapy with ATS in neonates and adults. METHODS: Meta-analysis: Clinical trials were identified by searching Medline, the Cochrane library and Current Contents. Published randomized studies in English or French comparing intrathecal therapy and intramuscular therapy (IMS) were analysed with Revman, R, and Stata software. Treatment effects were evaluated by relative risk (RR) between intrathecal vs. intramuscular administration. RESULTS: A total of 942 patients were included in 12 trials, 484 in the intrathecal group and 458 in the intramuscular one. The combined RR of mortality for intrathecal vs. IMS was 0.71 (95% CI, 0.62-0.81). The superiority of intrathecal therapy also emerged when the analysis was performed in subcategories of both adults and neonates and for high and low dose of intrathecal serotherapy. Intrathecal administration of ATS or TIG is more beneficial than intramuscular administration in the treatment of tetanus.     

Recovery from Severe Glucocorticoid-Induced Osteoporosis in an Adolescent Boy

An 18-yr-old boy presented with extreme back pain as the result of multiple vertebral fractures. At age 16 he had developed a tumor of the mesencephalon. A ventriculoperitoneal shunt was established surgically. One year later, he developed progressive neurologic deficits in his upper and lower limbs with an increase in the size of the tumor. He was treated by irradiation and high doses of glucocorticoids. Although the neurologic deficits progressively improved, he developed severe back pain resulting in complete immobilization for 3 mo in spite of neurologic recovery. Multiple vertebral fractures were diagnosed by X-ray. Bone density was extremely low (Z-score of -5.5 in the spine and -3.1 in the femoral neck). The patient was treated with calcium and vitamin D, calcitonin, bisphosphonates, physiotherapy, and progressive mobilization. Glucocorticoids were decreased and could be stopped as the neurologic deficits fully recovered. After 1 yr of treatment with intermittent i.v. pamidronate, bone density had increased by 40% in the spine and by 25% in the femoral neck despite growth arrest. He progressively recovered from back pain and is now, at age 20, fully ambulant, studying mechanical engineering, without neurologic sequelaes and free of glucocorticoids. Magnetic resonance imaging revealed that the tumor had disappeared. This case proves that treatment of symptomatic glucocorticoid-induced osteoporosis during puberty can be rewarding, even when multiple and invalidating vertebral fractures already exist.     

Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.     

Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients

BACKGROUND: Additive hemodynamic effects of combined blockade of the renin-angiotensin system by an angiotensin I converting enzyme inhibitor and an angiotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure. OBJECTIVE: To investigate whether the same additive hemodynamic effects occur in patients with hypertension and to verify the safety of such an approach. DESIGN: Multicenter, randomized, double-blind, parallel-group, pilot study. PATIENTS: 177 patients with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were included in the study. INTERVENTION: Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therapeutic regimen was compared with similar groups of patients who received either 50 mg losartan daily or 10 mg enalapril daily. MAIN OUTCOME MEASURES: 24-hour ambulatory mean DBP and clinic DBP measured at trough after 6 weeks of treatment. RESULTS: 24-hour ambulatory mean DBP did not significantly differ between treatment groups although the combination tended to lower BP more. The combination therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angiotensin I levels during blockade by the combination therapy were observed. This finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone. CONCLUSION: A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in patients with mild-to-moderate essential hypertension.     

Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist

Chemokines are proinflammatory cytokines that play a role in leukocyte migration and activation. Recent reports showed that RANTES (regulated on activation normal T-cell expressed and secreted chemokine), eotaxin, macrophage-derived chemokine (MDC), and stromal cell-derived factor-1 (SDF-1) are NH(2)-terminally truncated by the lymphocyte surface glycoprotein and protease CD26/dipeptidyl peptidase IV (CD26/DPP IV). Removal of the NH(2)-terminal dipeptide resulted in impaired inflammatory properties of RANTES, eotaxin, MDC, and SDF-1. The potential CD26/DPP IV substrate macrophage inflammatory protein-1beta (MIP-1beta) and the related chemokine, LD78alpha (ie, one of the MIP-1alpha isoforms), were not affected by this protease. However, CD26/DPP IV cleaved LD78beta, a most potent CCR5 binding chemokine and inhibitor of macrophage tropic human immunodeficiency virus-1 (HIV-1) infection, into LD78beta(3-70). Naturally truncated LD78beta(3-70), but not truncated MIP-1beta, was recovered as an abundant chemokine form from peripheral blood mononuclear cells. In contrast to all other chemokines processed by CD26/DPP IV, LD78beta(3-70) had increased chemotactic activity in comparison to intact LD78beta. With a minimal effective concentration of 30 pmol/L, LD78beta(3-70) became the most efficient monocyte chemoattractant. LD78beta(3-70) retained its high capacity to induce an intracellular calcium increase in CCR5-transfected cells. Moreover, on CCR1 transfectants, truncated LD78beta(3-70) was 30-fold more potent than intact LD78beta. Thus, CD26/DPP IV can exert not only a negative but also a positive feedback during inflammation by increasing the specific activity of LD78beta. CD26/DPP IV-cleaved LD78beta(3-70) is the most potent CCR1 and CCR5 agonist that retains strong anti-HIV-1 activity, indicating the importance of the chemokine-protease interaction in normal and pathologic conditions. (Blood. 2000;96:1674-1680)     

Treatment outcomes for human African Trypanosomiasis in the Democratic Republic of the Congo: analysis of routine program data from the world’s largest sleeping sickness control program

Objective To enable the human African trypanosomiasis (HAT) control program of the Democratic Republic of the Congo to generate data on treatment outcomes, an electronic database was developed. The database was piloted in two provinces, Bandundu and Kasai Oriental. In this study, we analysed routine data from the two provinces for the period 2006–2008. Methods Data were extracted from case declaration cards and monthly reports available at national and provincial HAT coordination units and entered into the database. Results Data were retrieved for 15 086 of 15 741 cases reported in the two provinces for the period (96%). Compliance with post‐treatment follow‐up was very poor in both provinces; only 25% had undergone at least one post‐treatment follow‐up examination, <1% had undergone the required four follow‐up examinations. Relapse rates among those presenting for follow‐up were high in Kasai (18%) but low in Bandundu (0.3%). Conclusions High relapse rates in Kasai and poor compliance with post‐treatment follow‐up in both provinces are important problems that the HAT control program urgently needs to address. Moreover, in analogy to tuberculosis control programs, HAT control programs need to adopt a recording and reporting routine that includes reporting on treatment outcomes.     

Is the content of guidelines/pathways a barrier for the integration of palliative Care in Chronic Heart Failure (CHF) and chronic pulmonary obstructive disease (COPD)? A comparison with the case of cancer in Europe

Background

There is a notable inequity in access to palliative care (PC) services between cancer and Chronic Heart Failure (CHF)/Chronic Obstructive Pulmonary Disease (COPD) patients which also translates into discrepancies in the level of integration of PC. By cross-examining the levels of PC integration in published guidelines/pathways for CHF/COPD and cancer in Europe, this study examines whether these discrepancies may be attributed to the content of the guidelines.

Design

A quantitative evaluation was made between integrated PC in published guidelines for cancer and CHF/COPD in Europe. The content of integrated PC in guidelines/pathways was measured using an 11 point integrated PC criteria tool (IPC criteria). A statistical analysis was carried out to detect similarities and differences in the level of integrated PC between the two groups.

Results

The levels of integration between CHF/COPD and cancer guidelines/pathways have been shown to be statistically similar. Moreover, the quality of evidence utilized and the date of development of the guidelines/pathways appear not to impact upon the PC integration in the guidelines.

Conclusion

In Europe, the empirically observed imbalance in integration of PC for patients with cancer and CHF/COPD may only partially be attributed to the content of the guidelines/pathways that are utilized for the PC implementation. Given the similarities detected between cancer and CHF/COPD, other barriers appear to play a more prominent role.