Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12).

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.

[Randomized clinical trial for primary care patients with neck pain: manual therapy versus electrical stimulation]. / Ensayo clínico aleatorizado en pacientes con cervicalgia mecánica en atención primaria: terapia manual frente a electroestimulación nerviosa transcutánea.

OBJECTIVE: To compare the effectiveness of manual therapy (MT) versus transcutaneous electrical nervous stimulation (TENS) in reducing the intensity of pain in patients with subacute or chronic neck pain (NP) attended at primary care physiotherapy units (PCPU). DESIGN: Randomised clinical trial. SETTING: Thirteen PCPU in 4 health districts of the Community of Madrid, Spain. PARTICIPANTS: Ninety patients with subacute or chronic NP attended. Lost after intervention: 3. INTERVENTIONS: At random, 47 patients were allocated to MT treatment and 43 to TENS. MAIN MEASUREMENTS: Social and demographic characteristics and prognosis variables in the intervention groups were measured. Intensity of pain before and after intervention was calculated by mean values on the analogue visual scale (present moment, average and worst pain of the last 2 weeks). Side-effects were also measured. RESULTS: Difference between before-and-after pain was 21.83 mm (95% CI, 13.71-29.95) for the group treated with Transcutaneous electrical nervous stimulation and 22.87 mm (95% CI, 17.11-28.64) for manual therapy. The difference in averages on comparing the 2 procedures for improvement was 1.04 (95% CI, -8.66% to 10.75%). CONCLUSIONS: TENS and MT significantly reduce patients' perceived intensity of pain, although there were no differences between the 2 groups.There are no conclusive results for the alternative physiotherapy treatments that determine a clear strategy of intervention.

Ensayo clínico aleatorizado en pacientes con cervicalgia mecánica en atención primaria: terapia manual frente a electroestimulación nerviosa transcutánea / Randomised clinical trial for primary care patients with neck pain: manual therapy versus electrical stimulation

Objetivo. Comparar la efectividad de la terapia manual frente a electroestimulación nerviosa transcutánea en la disminución de la intensidad del dolor en pacientes con cervicalgia mecánica subaguda o crónica atendidos en unidades de fisioterapia de atención primaria (UFAP). Diseño. Ensayo clínico aleatorio. Emplazamiento. Se incluyeron 13 UFAP de 4 áreas de salud de la Comunidad de Madrid. Participantes. Formaron parte del estudio 90 pacientes atendidos con cervicalgia mecánica subaguda o crónica. Se produjeron 3 pérdidas tras la intervención. Intervenciones. Se asignaron aleatoriamente 47 pacientes al tratamiento con terapia manual y 43 a recibir electroestimulación nerviosa transcutánea. Mediciones principales. Se midieron las características sociodemográficas y las variables pronóstico por grupo de intervención, así como la intensidad del dolor antes y después de la intervención con la media de los valores de la escala analógica visual (momento presente, promedio y peor dolor de las últimas 2 semanas) y los efectos adversos. Resultados. La diferencia en la intensidad del dolor antes-después fue de 21,83 mm (intervalo de confianza [IC] del 95%, 13,71-29,95) para el grupo tratado con electroestimulación nerviosa transcutánea y de 22,87 mm (IC del 95%, 17,11-28,64) para la terapia manual. La diferencia de medias comparando la mejoría obtenida con uno y otro procedimiento fue de 1,04 (IC del 95%, de -8,66 a 10,75). Conclusiones. Se ha observado una reducción en la intensidad del dolor percibida por los pacientes, si bien no se encontraron diferencias entre ambos tratamientos (electroestimulación nerviosa transcutánea y terapia manual). Este estudio no permite establecer la alternativa de tratamientos fisioterapéuticos en la cervicalgia mecánica atendida en atención primaria

Objective. To compare the effectiveness of manual therapy (MT) versus transcutaneous electrical nervous stimulation (TENS) in reducing the intensity of pain in patients with subacute or chronic neck pain (NP) attended at primary care physiotherapy units (PCPU). Design. Randomised clinical trial. Setting. Thirteen PCPU in 4 health districts of the Community of Madrid, Spain. Participants. Ninety patients with subacute or chronic NP attended. Lost after intervention: 3. Interventions. At random, 47 patients were allocated to MT treatment and 43 to TENS. Main measurements. Social and demographic characteristics and prognosis variables in the intervention groups were measured. Intensity of pain before and after intervention was calculated by mean values on the analogue visual scale (present moment, average and worst pain of the last 2 weeks). Side-effects were also measured. Results. Difference between before-and-after pain was 21.83 mm (95% CI, 13.71-29.95) for the group treated with Transcutaneous electrical nervous stimulation and 22.87 mm (95% CI, 17.11-28.64) for manual therapy. The difference in averages on comparing the 2 procedures for improvement was 1.04 (95% CI, -8.66% to 10.75%). Conclusions. TENS and MT significantly reduce patients' perceived intensity of pain, although there were no differences between the 2 groups.There are no conclusive results for the alternative physiotherapy treatments that determine a clear strategy of intervention