The role of mobile phones in improving vaccination rates in travelers

RATIONALE: Noncompliance with vaccination schedules undermines the potential benefits of immunization. The purpose of this study was to evaluate whether a reminder of the next vaccine dose sent by the Short Messaging Service (SMS) to the vaccinee's mobile phone increases compliance with hepatitis A + B and hepatitis A vaccination schedule. SUBJECTS AND METHODS: In this experimental, controlled study, the study group comprised travelers who went to the Internacional-Clínic Vaccination Centre between the 1st June and 30th September of 2001 for the standard immunization schedule against hepatitis A + B and against hepatitis A. Trained health-care workers entered the data into a computer to generate text messages reminding vaccinees of their scheduled doses. Two control groups, one from the same period of the same year including travelers from the third office (Control 2001) and the second, all travelers seen in the same period of the previous year (Control 2000), were used. RESULTS: For the second hepatitis A + B dose, compliance in the study group (Message Groups) was 88.4% (83.3-92.2); in the Control 2001, 80.7% (76.3-84.4, relative risk [RR] 1.10 [1.02-1.17]); and in the Control 2000, 77.2% (73.3-80.5, RR 1.15 [1.07-1.22]). For the third hepatitis A + B vaccine dose, results were 47.1% (40.5-53.8); 26.9% (22.8-31.7, RR 1.75 [1.41-2.17]); and 23.6% (20.1-27.4, RR 2.00 [1.63-2.45]), respectively. As for the hepatitis A vaccine, compliance rates for the second dose were 27.7% (23.9-31.9); 16.4% (14.4-18.6, RR 1.69 [1.40-2.04]); and 13.2% (11.6-14.9, RR 2.10 [1.75-2.54]); respectively. CONCLUSIONS: SMS seems to be an effective tool for increasing compliance with vaccination schedules.     

Different Fish-Eating Habits and Cytokine Production in Chronic Urticaria with and without Sensitization against the Fish-Parasite Anisakis simplex

BackgroundAnisakis simplex sensitization has been associated with acute, but also with chronic urticaria. The objective of this study is to characterize chronic urticaria with (CU +) and without sensitization (CU-) against the ubiquitous fish parasite A. simplex in a transversal and longitudinal evaluation.Methods16 CU + and 22 CU- patients were included and assessed for Urticaria activity score (UAS), fish-eating habits by standardized questionnaire and cytokine production (assessed by flow cytometric bead-based array) of peripheral blood mononuclear cells after stimulation with A. simplex extract or Concanavalin A (Con A). Patients were randomly put on a fish-free diet for three months and UAS, as well as cytokine production were again assessed. A difference of ≥ 1 in UAS was defined as improvement.ResultsThere was no difference in UAS in both groups. Anisakis induced IL-2, IL-4 and IFN-γ production was higher in CU +. Con A induced IL-6 and IL-10 production was higher in CU +. CU + was associated with higher total fish intake, whereas CU- was associated with oily fish intake. The correlation of UAS was positive with oily fish, but negative with total fish intake.There was a better UAS-based prognosis in CU + without diet. Improvement was associated with higher Con A induced IL-10/IFN-γ as well as IL-10/IL-6 ratios. Further, previous higher oily fish intake was associated with improvement.ConclusionsOur data confirm the different clinical and immunological phenotype of CU +. Our results show a complex relationship between fish-eating habits, cytokine production and prognosis, which could have important consequences in dietary advice in patients with CU. When encountering A. simplex sensitization, patients should not be automatically put on a diet without fish in order to reduce contact with A. simplex products.     

Echocardiographic assessment of pulmonary arterial pressure in the follow-up of patients with pulmonary embolism

Background

Echocardiography remains a clinically useful screening test for chronic thromboembolic pulmonary hypertension (CTEPH) in patients with a history of pulmonary embolism (PE). To devise an effective screening strategy, the definition of a high-risk group is necessary.

Methods

We examined a total of 744 patients with acute symptomatic pulmonary embolism (PE) who were enrolled in a Spanish multicenter study. Patients were monitored every 6 months during the first two years, and then once a year thereafter. Transthoracic echocardiography was used to screen patients with a clinical suspicion of CTEPH during follow-up. Pulmonary arterial hypertension was defined as an estimated pulmonary artery systolic pressure (PAP) > 50 mm Hg. The index thromboembolic episode was considered severe if: (a) the patient was immobilized for medical reasons; or (b) systolic blood pressure was less than 90 mm Hg; or (c) troponin T values were above the reference range.

Results

The incidence of PAP > 50 mm Hg at 36 months was 8.3% (95% confidence interval = 4.6%-14.5%). Statistical analysis showed a highly significant association between a severe index thromboembolic episode and the subsequent detection of PAP > 50 mm Hg on echocardiography, with high positive likelihood ratio (2.40) and negative predictive value (> 0.97).

Conclusions

Patients with a severe index thromboembolic episode would constitute a high-risk group for the development of CTEPH. This group of patients should be subjected to a strict follow-up protocol.     

5-Fluorouracil derivatives: a patent review

INTRODUCTION: The fluorinated analog of uracil 5-FU is an antimetabolite, active against a wide range of solid tumors. The main mechanism of action consists in interfering with DNA synthesis and mRNA translation. However, patients treated with 5-FU display several side effects, a result of its nonspecific cytotoxicity for tumor cells. Numerous modifications of the 5-FU structure have been performed in order to overcome these disadvantages. AREAS COVERED: In this review, the metabolic pathways, pharmacokinetics and clinical pharmacology of 5-FU are briefly introduced. Moreover, several derivatives developed and patented, including oral 5-FU prodrugs and combinations with other active compounds, are presented. Finally, new innovative methods for administration and vehiculization of 5-FU and its derivatives are described. EXPERT OPINION: The search for less toxic 5-FU derivatives, which diminish or circumvent some of its disadvantages, has allowed the development of selective antitumor prodrugs and novel methods for tissue-specific drug delivery. Although some of these oral prodrugs are being used clinically, either alone or in combination therapy with other anticancer agents, it seems that the potential of personalized medicine, including pharmacogenomics and targeted therapy with novel 5-FU derivatives, will improve the management and clinical responses of patients treated with 5-FU-based therapy.     

Poly(butylcyanoacrylate) and Poly(ε-caprolactone) Nanoparticles Loaded with 5-Fluorouracil Increase the Cytotoxic Effect of the Drug in Experimental Colon Cancer

The clinical use of 5-fluorouracil, one of the drugs of choice in colon cancer therapy, is limited by a nonuniform oral absorption, a short plasma half-life, and by the development of drug resistances by malignant cells. We hypothesized that the formulation of biodegradable nanocarriers for the efficient delivery of this antitumor drug may improve its therapeutic effect against advanced or recurrent colon cancer. Hence, we have engineered two 5-fluorouracil-loaded nanoparticulate systems based on the biodegradable polymers poly(butylcyanoacrylate) and poly(ε-caprolactone). Drug incorporation to the nanosystems was accomplished by entrapment (encapsulation/dispersion) within the polymeric network during nanoparticle synthesis, i.e., by anionic polymerization of the monomer and interfacial polymer disposition, respectively. Main factors determining 5-fluorouracil incorporation within the polymeric nanomatrices were investigated. These nanocarriers were characterized by high drug entrapment efficiencies and sustained drug-release profiles. In vitro studies using human and murine colon cancer cell lines demonstrated that both types of nanocarriers significantly increased the antiproliferative effect of the encapsulated drug. In addition, both nanoformulations produced in vivo an intense tumor growth inhibition and increased the mice survival rate, being the greater tumor volume reduction obtained when using the poly(ε-caprolactone)-based formulation. These results suggest that these nanocarriers may improve the antitumor activity of 5-fluorouracil and could be used against advanced or recurrent colon cancer.KEY WORDS: 5-fluorouracil, colon cancer, poly(butylcyanoacrylate), poly(ε-caprolactone), polymeric nanoparticles     

Reactogenicity profile of a combined hepatitis A and B vaccine in clinical practice: a naturalistic study in adult travellers

A prospective observational naturalistic study was conducted to assess the reactogenicity of the combined hepatitis A and hepatitis B (HAB) vaccine in a real-life setting. All healthy candidates for HAB vaccination attending an adult vaccination centre between October 1998 and February 2000 were invited to participate in the study. A follow-up diary card was provided to subjects to record local and general symptoms during a 4-day follow-up. Intensity was graded from 1 to 3. Redness was recorded as presence or absence. Fever was defined as axillar temperature > or =37.5 degrees C and grade 3 >39.0 degrees C. For all other symptoms, grade 3 was defined as an adverse reaction preventing normal everyday activities; 998 subjects (74% females), mean age (+/-S.D.) of 23 years (+/-4.5) (range: 11-54 years) agreed to participate. At first immunization 92% were <30 years old. Grade 3 pain and swelling was recorded in 1.2% and 0.3% of local symptom sheets completed, respectively; 438 subjects received the HAB vaccine alone (group 1) whereas 560 received at least one concomitant vaccine (group 2). In 45%, 27%, 18% and 10% of subjects the HAB vaccine was coadministered with 1, 2, 3 or 4 to 6 vaccines (mainly Td adult-type, typhoid, MMR and IPV vaccine). Grade 3 pain and swelling were recorded in 1.2% & 0.3% of symptom sheets (SS), respectively. In group 1, any fever and grade 3 fever was recorded in 3.5% and 0.1% of SS. Group 1 versus 2 had a lower risk for any fatigue (p=0.0002; OR=0.617) and any malaise (p=0.0076; OR=0.693) but not for grade 3 symptoms. In conclusion, our study showed that the HAB vaccine is well tolerated in adults either alone or coadministered with other vaccines in the routine clinical practice.