Drug interactions detected by a computer-assisted prescription system in primary care patients in Spain: MULTIPAP study.

BACKGROUND: Drug interactions increase the risk of treatment failure, intoxication, hospital admissions, consultations and mortality. Computer-assisted prescription systems can help to detect interactions. OBJECTIVES: To describe the drug-drug interaction (DDI) and drug-disease interaction (DdI) prevalence identified by a computer-assisted prescription system in patients with multimorbidity and polypharmacy. Factors associated with clinically relevant interactions were analysed. METHODS: Observational, descriptive, cross-sectional study in primary health care centres was undertaken in Spain. The sample included 593 patients aged 65-74 years with multimorbidity and polypharmacy participating in the MULTIPAP Study, recruited from November 2016 to January 2017. Drug interactions were identified by a computer-assisted prescription system. Descriptive, bivariate, and multivariate analyses with logistic regression models and robust estimators were performed. RESULTS: Half (50.1% (95% CI 46.1-54.1)) of the patients had at least one relevant DDI and 23.9% (95% CI 18.9-25.6) presented with a DdI. Non-opioid-central nervous system depressant drug combinations and benzodiazepine-opioid drug combinations were the two most common clinically relevant interactions (10.8% and 5.9%, respectively). Factors associated with DDI were the use of more than 10 drugs (OR 11.86; 95% CI 6.92-20.33) and having anxiety/depressive disorder (OR 1.98; 95% CI 1.31-2.98). Protective factors against DDI were hypertension (OR 0.62; 95% CI 0.41-0.94), diabetes (OR 0.57; 95% CI 0.40-0.82), and ischaemic heart disease (OR 0.43; 95% CI 0.25-0.74). CONCLUSION: Drug interactions are prevalent in patients aged 65-74 years with multimorbidity and polypharmacy. The clinically relevant DDI frequency is low. The number of prescriptions taken is the most relevant factor associated with presenting a clinically relevant DDI.

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12).

OBJECTIVES: To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. DESIGN: Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). PARTICIPANTS: 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. INTERVENTIONS: The 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 OUTCOMES: Serum 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. RESULTS: The 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. CONCLUSIONS: Oral 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 NUMBERS: NCT01476007; EUDRACT (2010-024129-20).

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.

Patient preferences and treatment safety for uncomplicated vulvovaginal candidiasis in primary health care.

BACKGROUND: Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial. METHODS/DESIGN: This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference. DISCUSSION: Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.

[Usefulness of a glaucoma and ocular hypertension screening strategy in primary care]. / Utilidad de una estrategia de cribado de hipertensión ocular y glaucoma en atención primaria.

OBJECTIVES: To evaluate the usefulness of a glaucoma and intraocular hypertension screening strategy for new cases detected. To evaluate the acceptability of taking intra-ocular pressure (IOP) and the appearance of side effects. DESIGN: Cross-sectional, descriptive study. SETTING: An urban health centre and the ophthalmology clinic of its main hospital. PARTICIPANTS: A total of 2044 patients aged over 40, 63.5% women and 36.5% men, with a mean age of 61.23 (SD, 11.42). They were selected by consecutive sampling from patients who visited the health centre over a 9-month period. Subjects diagnosed with glaucoma, ocular hypertension (OH), conjunctivitis, or corneal pathology were excluded. INTERVENTIONS: Taking of IOP with Tonopen XL in primary care. Subjects with IOP > or = 21 mm Hg were referred to ophthalmology. In these patients, IOP was measured with Goldmann, and patients with confirmed OH received ophthalmoscopy and campimetry. MAIN MEASUREMENTS: Percentage of subjects with glaucoma, suspected glaucoma, and OH confirmed in ophthalmology. Positive predictive value (PPV) for OH. RESULTS: One hundred subjects with OH were detected (4.89%; 95% CI, 3.93%-5.85%), of whom 21 were diagnosed with glaucoma (1.04%; 95% CI, 0.57-1.49) and 10 with suspected glaucoma (0.49%; 95% CI, 0.16-0.82). The PPV for OH was 44.27%. The acceptability of the test was 98.09%. No patients presented with side-effects following the taking of their IOP. CONCLUSIONS: The strategy evaluated is useful in terms of the number of subjects with glaucoma and OH detected. The acceptability of taking IOP with Tonopen XL was high.

Utilidad de una estrategia de cribado de hipertensión ocular y glaucoma en atención primaria / Usefulness of a glaucoma and ocular hypertension screening strategy in primary care

Objetivos. Evaluar la utilidad de una estrategia de cribado de glaucoma e hipertensión ocular (HTO) medida como número de casos detectados. Evaluar la aceptabilidad de la toma de presión intraocular (PIO) y la aparición de efectos secundarios. Diseño. Estudio descriptivo transversal. Emplazamiento. Centro de salud urbano y consulta de oftalmología del hospital de referencia. Participantes. En total, 2.044 pacientes mayores de 40 años, seleccionados por muestreo consecutivo entre los que consultaron en el centro de salud durante 9 meses. Se excluyeron los sujetos diagnosticados de glaucoma, HTO, conjuntivitis o enfermedad corneal. Intervenciones. Toma de PIO con Tonopen XL en atención primaria. Se remitió a oftalmología a los sujetos con una PIO ≥ 21 mmHg. En éstos se midió la PIO con la prueba de Goldmann y, en los que se confirmó la HTO, se realizaron una oftalmoscopia y una campimetría. Mediciones principales. Porcentaje de sujetos con glaucoma, sospecha de glaucoma e HTO confirmada en oftalmología. Valor predictivo positivo (VPP) para HTO. Resultados. Se detectaron 100 sujetos con HTO (4,89%; intervalo de confianza [IC] del 95%, 3,93-5,85%), de los que 21 fueron diagnosticados de glaucoma (1,04%; IC del 95%, 0,57-1,49%) y 10 de sospecha de glaucoma (0,49%; IC del 95%, 0,16-0,82). El VPP para HTO fue del 44,27%. La aceptabilidad de la prueba fue del 98,09%. Ningún paciente presentó efectos secundarios tras la toma de la PIO. Conclusiones. La estrategia evaluada es útil en cuanto al porcentaje de sujetos con glaucoma e HTO detectados. La aceptabilidad de la toma de la PIO con Tonopen XL es alta

Objectives. To evaluate the usefulness of a glaucoma and intraocular hypertension screening strategy for new cases detected. To evaluate the acceptability of taking intra-ocular pressure (IOP) and the appearance of side effects. Design. Cross-sectional, descriptive study. Setting. An urban health centre and the ophthalmology clinic of its main hospital. Participants. A total of 2044 patients aged over 40, 63.5% women and 36.5% men, with a mean age of 61.23 (SD, 11.42). They were selected by consecutive sampling from patients who visited the health centre over a 9-month period. Subjects diagnosed with glaucoma, ocular hypertension (OH), conjunctivitis, or corneal pathology were excluded. Interventions. Taking of IOP with Tonopen XL in primary care. Subjects with IOP 21 mm Hg were referred to ophthalmology. In these patients, IOP was measured with Goldmann, and patients with confirmed OH received ophthalmoscopy and campimetry. Main measurements. Percentage of subjects with glaucoma, suspected glaucoma, and OH confirmed in ophthalmology. Positive predictive value (PPV) for OH. Results. One hundred subjects with OH were detected (4.89%; 95% CI, 3.93%-5.85%), of whom 21 were diagnosed with glaucoma (1.04%; 95% CI, 0.57-1.49) and 10 with suspected glaucoma (0.49%; 95% CI, 0.16-0.82). The PPV for OH was 44.27%. The acceptability of the test was 98.09%. No patients presented with side-effects following the taking of their IOP. Conclusions. The strategy evaluated is useful in terms of the number of subjects with glaucoma and OH detected. The acceptability of taking IOP with Tonopen XL was high