The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following ...protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency.
The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3-8,and 1 mg/month in weeks 9-52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses.
The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment.
This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.
ObjectivesTo compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency.DesignPragmatic, randomised, non-inferiority, multicentre ...trial in 22 primary healthcare centres in Madrid (Spain).Participants283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm.InterventionsThe IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52.Main outcomesSerum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction.ResultsThe follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route.ConclusionsOral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Trial registration numbersNCT 01476007; EUDRACT (2010-024129-20).
To determine the crude and sex- and age-adjusted prevalence rates of atherogenic dyslipidemia (AD) and low HDL-cholesterol levels (low-HDLc), and to assess their associations with cardiovascular risk ...factors, chronic kidney disease, cardiovascular and cardiometabolic diseases.
Population-based cross-sectional study conducted in Primary Care, with randomly selected adult subjects. The AD was considered if the patients had hypertriglyceridemia (triglycerides ≥150 mg/dL) and low-HDLc (<40 mg/dL men; <50 mg/dL women). Crude and sex- and age-adjusted prevalence rates were determined, and univariate and multivariate analysis were performed to assess related cardiometabolic factors.
Study population with 6,588 adults (55.9% women) with mean age 55.1 (±17.5) years. The mean HDLc levels were 49.2 (±12.6) mg/dL in men and 59.2 (±14.7) mg/dL in women. The crude prevalence rates of low-HDLc and AD were 30.8% (95%CI: 29.7–31.9), and 14.3% (95%CI: 13.5–15.2), respectively. The adjusted prevalence rates of low-HDLc were 28.0% in men and 31.0% in women, and AD were 16.4% in men and 10.6% in women. Seventy-three percent of the population with AD had high or very high cardiovascular risk. The independent factors associated with low HDLc or with AD were diabetes, smoking, abdominal obesity, and obesity. The major factors associated with low HDLc and AD were hypertriglyceridemia and diabetes, respectively.
Almost a third of the adult population had low HDL-C and half of them met AD criteria. Cardiometabolic factors were associated with low HDL-C and AD, highlighting HTG with low HDLc, and DM with AD
Determinar las prevalencias ajustadas por edad y sexo de concentraciones bajas de colesterol HDL (cHDL-bajo) y de dislipidemia aterogénica (DA), y valorar sus asociaciones con factores de riesgo cardiovascular, enfermedad renal crónica, enfermedades cardiovasculares y cardiometabólicas.
Estudio observacional transversal de base poblacional realizado en Atención Primaria, con sujetos adultos seleccionados aleatoriamente. Se consideró DA si los pacientes tenían hipertrigliceridemia (triglicéridos ≥150 mg/dL) y cHDL-bajo (<40 mg/dL hombres; <50 mg/dL mujeres). Se determinaron las tasas de prevalencia crudas y ajustadas por edad y sexo, y se realizó análisis univariado y multivariante para evaluar los factores cardiometabólicos relacionados.
Población de estudio con 6.588 adultos (55,9% mujeres) con edad media 55,1 (±17,5) años. Las medias de cHDL fueron 49,2 (±12,6) mg/dL en hombres y 59,2 (±14,7) mg/dL en mujeres. Las prevalencias crudas de cHDL-bajo y de DA fueron 30,8% (IC95%: 29,7–31,9), y 14,3% (IC95%: 13,5–15,2), respectivamente. Las prevalencias ajustadas de cHDL-bajo fueron 28,0% en hombres y 31,0% en mujeres, y de DA fueron 16,4% en hombres y 10,6% en mujeres. El 73% de la población con DA tenía riesgo cardiovascular alto o muy alto. Los factores independientes asociados con cHDL-bajo o con DA fueron diabetes, tabaquismo, obesidad abdominal y obesidad. Los principales factores asociados con cHDL-bajo y con DA fueron hipertrigliceridemia y diabetes, respectivamente.
Casi un tercio de la población adulta presentaba cHDL-bajo y la mitad de ellos cumplía criterios de DA. Los factores cardiometabólicos se asociaban con cHDL-bajo y DA, destacando la HTG con el cHDL-bajo, y la DM con la DA.
Wells syndrome, also known as eosinophilic cellulitis, is a rare dermatosis with approximately 200 cases previously described in the literature. Here, we present a case of a patient with multiple ...sclerosis with Wells syndrome induced by dimethyl fumarate (DMF).
A 41-year-old Caucasian woman was treated with DMF in July 2021. One week later, she experienced itching on her upper and lower right arm, followed by the appearance of erythematous plaques covered with vesicles. The complete blood count showed an increased eosinophil count of up to 2,000 µL. The histological images demonstrated dermal eosinophil infiltration concordant with Wells syndrome. The clinical course was benign, with complete resolution of the lesions and normalization of the eosinophil count within four weeks. Administration of corticosteroids was not necessary.
Eosinophilia is rare in patients with multiple sclerosis treated with DMF and usually does not require dosage adjustments. Although clinical manifestations of eosinophilia in these patients are very rare, it is important for practitioners to recognize the symptoms. Many neuroleptic drugs can induce eosinophilia and systemic symptoms; therefore, physicians must be aware of the risks associated with DMF and neuroleptic drugs, particularly for quetiapine, which contains fumarate.
To evaluate the cytotoxicity of 15% citric acid, 5% phosphoric acid and 2.5% NaOCl on cultured fibroblasts using MTT colorimetric assay.
Irrigating solutions of 5% phosphoric acid, 15% citric acid, ...and 2.5% NaOCl, diluted at 0.1% and 0.5%, were applied to cell cultures of 3T3L1 fibroblasts. The cell viability was determined by means of MTT colorimetric assay after a period of 1, 6 and 24 hours. Percentages of cell viability were analyzed using the Kruskal-Wallis test for global comparisons and the Mann-Whitney U-test for pairwise comparisons.
The percentage of cell viability diminished progressively over a 24 hour period in all solutions at both dilutions. At 0.1% dilution, 2.5% NaOCl (63.39%) and 15% citric acid (53.91%) showed the highest percentage of cell viability (p=0.083). At 0.5% dilution, 2.5% NaOCl again showed the highest cell viability value (48.51%).
The irrigating solution with the highest percentage of cell viability was 2.5% NaOCl at both 0.1% and 0.5% dilutions. A very low percentage of cell viability was obtained with 15% citric acid and 5% phosphoric acid at 0.5% dilution.
To evaluate, in vitro, the antimicrobial activity and biofilm formation of three chlorhexidine varnishes in four E. faecalis strains: E. faecalis ATCC 29212, E. faecalis EF-D1 (from failed endodontic ...treatment), E. faecalis 072 (cheese) and E. faecalis U-1765 (nosocomial infection), and one E. durans strain (failed endodontic treatment).
The direct contact test was used to study the antimicrobial activity. Bacterial suspensions were exposed for one hour to EC40, Cervitec (CE) and Cervitec Plus (CEP) varnishes. "Eradication " was defined as 100% bacterial kill. The formation of enterococci biofilms was tested on the surface of the varnishes after 24 hours of incubation and expressed as percentage of biofilm reduction.
EC40 eradicated all strains except E. faecalis ATCC 29212, where 98.78% kill was achieved. CE and CEP showed antimicrobial activity against all the strains, but most clearly against E. durans and E. faecalis 072. EC40 completely inhibited the formation of biofilm of E. faecalis ATCC 29212, E. faecalis 072 and E. durans. CE and CEP led to over 92% of biofilm reduction, except in the case of E. faecalis U-1765 on CEP (76.42%).
The three varnishes studied were seen to be effective in killing the tested strains of enterococci and in inhibiting the formation of biofilm, the best results being observed with EC40.
To assess the influence of final irrigation protocols with chlorhexidine in the coronal leakage of Enterococcus faecalis in filled root canals.
Seventy single-root canals from extracted teeth were ...prepared using ProTaper instruments. The irrigation protocol accomplished an alternating irrigation with 5 mL of 2.5% sodium hypochlorite (NaOCI) and 17% EDTA between each file. The teeth were randomly divided into four experimental groups (n=15) according to the final irrigation regimen: group 1, without final irrigation; group 2, irrigation with 10 mL 2.0% chlorhexidine (CHX); group 3, with a final application of EC40™; and group 4, irrigation with the combination (1:1) of 0.2% CHX + 0.1% cetrimide (CTR). All the teeth were mounted in a two-chamber apparatus and the coronal access was exposed to E. faecalis. The presence of turbidity in the BHI broth over a period of 180 days was observed. The Friedman test was used for statistical analysis.
EC40™ varnish showed the least leakage at 180 days, and was statistically similar to 2% CHX. No significant differences were observed between the group without final irrigation and the 2% CHX group or 0.2% CHX + 0.1% CTR.
In this ex vivo study, EC40™ showed the longest delayed coronal leakage of E. faecalis, although without significant differences from 2% CHX.
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