"Maternal Vaccination Greatly Depends on Your Trust in the Healthcare System": A Qualitative Study on the Acceptability of Maternal Vaccines among Pregnant Women and Healthcare Workers in Barcelona, Spain.

The World Health Organization (WHO) identified vaccine hesitancy as one of the top 10 threats to global health in 2019. Health promotion and education have been seen to improve knowledge and uptake of vaccinations in pregnancy. This qualitative study was conducted based on phenomenology, a methodological approach to understand first-hand experiences, and grounded theory, an inductive approach to analyse data, where theoretical generalisations emerge. Data were collected through semi-structured interviews with pregnant women attending antenatal care services and healthcare workers (HCWs) in Barcelona, Spain. Interviews were audio-recorded, transcribed, and coded, and notes were taken. Inductive thematic analysis was performed, and data were manually coded. Pertussis was reported as the most trusted vaccine among pregnant women due to its long-standing background as a recommended vaccine in pregnancy. The influenza vaccine was regarded as less important since it was perceived to cause mild disease. The COVID-19 vaccine was the least trustworthy for pregnant women due to uncertainties about effectiveness, health effects in the mid- and long-term, the fast development of the vaccine mRNA technology, and the perceptions of limited data on vaccine safety. However, the necessity to be vaccinated was justified by pregnant women due to the exceptional circumstances of the COVID-19 pandemic. The recommendations provided by HCW and the established relationship between the HCW, particularly midwives, and pregnant women were the main factors affecting decision-making. The role of mass media was perceived as key to helping provide reliable messages about the need for vaccines during pregnancy. Overall, vaccines administered during pregnancy were perceived as great tools associated with better health and improved quality of life. Pregnancy was envisioned as a vulnerable period in women's lives that required risk-benefits assessments for decision-making about maternal vaccinations. A holistic approach involving the community and society was considered crucial for health education regarding maternal vaccines in support of the work conducted by HCWs.

Interindividual variability in response to protein and fish oil supplementation in older adults: a randomized controlled trial.

BACKGROUND: Precision nutrition is highly topical. However, no studies have explored the interindividual variability in response to nutrition interventions for sarcopenia. The purpose of this study was to determine the magnitude of interindividual variability in response to two nutrition supplementation interventions for sarcopenia and metabolic health, after accounting for sources of variability not attributable to supplementation. METHODS: A 24 week, randomized, double-blind, placebo-controlled trial tested the impact of leucine-enriched protein (LEU-PRO), LEU-PRO plus long-chain n-3 PUFA (LEU-PRO+n-3) or control (CON) supplementation in older adults (n = 83, 71 ± 6 years) at risk of sarcopenia. To estimate the true interindividual variability in response to supplementation (free of the variability due to measurement error and within-subject variation), the standard deviation of individual responses (SDR ) was computed and compared with the minimally clinically important difference (MCID) for appendicular lean mass (ALM), leg strength, timed up-and-go (TUG), and serum triacylglycerol (TG) concentration. Clinically meaningful interindividual variability in response to supplementation was deemed to be present when the SDR positively exceeded the MCID. The probability that individual responses were clinically meaningful, and the phenotypic, dietary, and behavioural determinants of response to supplementation were examined. RESULTS: The SDR was below the MCID for ALM (LEU-PRO: -0.12 kg [90% CI: -0.38, 0.35], LEU-PRO+n-3: -0.32 kg [-0.45, 0.03], MCID: 0.21 kg), TUG (LEU-PRO: 0.58 s [0.18, 0.80], LEU-PRO+n-3: 0.73 s [0.41, 0.95], MCID: 0.9 s) and TG (LEU-PRO: -0.38 mmol/L [-0.80, 0.25], LEU-PRO+n-3: -0.44 mmol/L [-0.63, 0.06], MCID: 0.1 mmol/L), indicating no meaningful interindividual variability in response to either supplement. The SDR exceeded the MCID (19 Nm) for strength in response to LEU-PRO (25 Nm [-29, 45]) and LEU-PRO+n-3 (23 Nm [-29, 43]) supplementation but the effect was uncertain, evidenced by wide confidence intervals. In the next stage of analysis, similar proportions of participant responses were identified as very likely, likely, possibly, unlikely, and very unlikely to represent clinically meaningful improvements across the LEU-PRO, LEU-PRO+n-3, and CON groups (P > 0.05). Baseline LC n-3 PUFA status, habitual protein intake, and numerous other phenotypic and behavioural factors were not determinants of response to LEU-PRO or LEU-PRO+n-3 supplementation. CONCLUSIONS: Applying a novel, robust methodological approach to precision nutrition, we show that there was minimal interindividual variability in changes in ALM, muscle function, and TG in response to LEU-PRO and LEU-PRO+n-3 supplementation in older adults at risk of sarcopenia.

Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n-3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Leucine-enriched protein (LEU-PRO) and long-chain (LC) n-3 (ω-3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. OBJECTIVE: The impact of LEU-PRO supplementation alone and combined with LC n-3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. METHODS: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n-3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n-3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). RESULTS: Neither LEU-PRO nor LEU-PRO+n-3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: -7.1 Nm; 95% CI: -12.5, -1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n-3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n-3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n-3 postsupplementation compared with CON (all P < 0.05). CONCLUSIONS: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n-3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.

[Chronic diseases and multimorbidiy in patients with toxic oil syndrome: a comparative study with general population.] / Enfermedades crónicas y multimorbilidad en pacientes con síndrome de aceite tóxico: estudio comparativo con población general.

OBJECTIVE: Toxic oil syndrome is a multisystemic disease that arose in 1981 due to the ingestion of contaminated rapeseed oil. Previous studies have found a higher prevalence of cardiovascular risk factors in these patients. The aim of this study was to analyze the differences in the prevalence of chronic diseases among a population affected by Toxic oil syndrome compared with a reference population in the Community of Madrid. METHODS: Cross-sectional observational study of patients with a registry diagnosed with Toxic oil syndrome in the primary care medical record and a reference sample without Toxic oil syndrome matched by age group and sex. Sociodemographic variables, cardiovascular risk factors, cardiovascular and cerebrovascular disease, anxiety, depression, asthma, chronic obstructive pulmonary disease, and low back pain, and multimorbidity (≥2 chronic diseases) were assesed. Descriptive and multivariate analysis was performed to study the association between morbidity and Toxic oil syndrome. RESULTS: 3,527 patients (1,394 Toxic oil syndrome) were included with a mean age of 66 (SD14) years, 71% women. Patients with a diagnosis of SAT were more likely to present multimorbidity (OR 1.36; 95%CI: 1.10-1.45), diabetes (OR 1.55; 95%CI: 1.29-1.86), complicated hypertension (OR 1.77; IC95%: 1.31-2.39), heart attack (OR 2.23; 95%CI: 1.47-3.38), depression (OR 1.39; 95%CI: 1.17-1.66) and asthma (OR 1.56; 95%CI: 1.23-1.97). The prevalence of anxiety was lower in TOS (OR 0.35; 95% CI: 0.18-0.69) as well as low back pain (OR 0.77; 95%CI: 0.65-0.91). CONCLUSIONS: Patients with toxic oil syndrome have a higher frequency of chronic diseases and mutimorbidity compared to the general population of the same sex and age.

OBJETIVO: El síndrome del aceite tóxico es una enfermedad multisistémica que surgió en 1981 debido a la ingesta de aceite de colza contaminado. Estudios previos han encontrado en estos pacientes una mayor prevalencia de factores de riesgo cardiovascular. El objetivo de este estudio fue analizar las posibles diferencias en prevalencia de morbilidad crónica entre una población afectada por síndrome de aceite tóxico comparada con una población de referencia en la Comunidad de Madrid. METODOS: Estudio observacional transversal de pacientes diagnosticados de síndrome del aceite tóxico en la historia clínica de atención primaria y una muestra de referencia sin síndrome del aceite tóxico apareados por grupo de edad y sexo. Se recogieron variables sociodemográficas, factores de riesgo cardiovascular, enfermedad cardiovascular y cerebrovascular, ansiedad, depresión, asma, enfermedad pulmonar obstructiva crónica, lumbalgia y multimorbilidad (≥2 enfermedades crónicas). Se realizó análisis descriptivo y multivariante para estudiar la asociación entre morbilidad y síndrome del aceite tóxico. RESULTADOS: Se incluyeron 3.527 pacientes (1.394 SAT) con una edad media de 66 (14) años, el 71% mujeres. Los pacientes con diagnóstico de síndrome del aceite tóxico tuvieron mayor probabilidad de presentar multimorbilidad (OR 1,36; IC95%: 1,10-1,45), diabetes (OR 1,55; IC95%: 1,29-1,86), hipertensión arterial complicada (OR 1,77; IC95%: 1,31-2,39), infarto (OR 2,23; IC95%: 1,47-3,38), depresión (OR 1,39; IC95%: 1,17-1,66) y asma (OR 1,56; IC95%: 1,23-1,97). La prevalencia de ansiedad fue menor (OR 0,35; IC95%: 0,18-0,69) así como de lumbalgia (OR 0,77; IC95%: 0,65-0,91). CONCLUSIONES: Los pacientes con síndrome de aceite tóxico presentan una mayor frecuencia de enfermedades crónicas y mutimorbilidad comparado con población general del mismo sexo y edad.

Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways.

Major Depression is a severe psychiatric condition with a still poorly understood etiology. In the last years, evidence supporting the neuroinflammatory hypothesis of depression has increased. In the current clinical scenario, in which the available treatments for depression is far from optimal, there is an urgent need to develop fast-acting drugs with fewer side effects. In this regard, recent pieces of evidence suggest that cannabidiol (CBD), the major non-psychotropic component of Cannabis sativa with anti-inflammatory properties, appears as a drug with antidepressant properties. In this work, CBD 30 mg/kg was administered systemically to mice 30 min before lipopolysaccharide (LPS; 0.83 mg/kg) administration as a neuroinflammatory model, and behavioral tests for depressive-, anhedonic- and anxious-like behavior were performed. NF-ĸB, IκBα and PPARγ levels were analyzed by western blot in nuclear and cytosolic fractions of cortical samples. IL-6 and TNFα levels were determined in plasma and prefrontal cortex using ELISA and qPCR techniques, respectively. The precursor tryptophan (TRP), and its metabolites kynurenine (KYN) and serotonin (5-HT) were measured in hippocampus and cortex by HPLC. The ratios KYN/TRP and KYN/5-HT were used to estimate indoleamine 2,3-dioxygenase (IDO) activity and the balance of both metabolic pathways, respectively. CBD reduced the immobility time in the tail suspension test and increased sucrose preference in the LPS model, without affecting locomotion and central activity in the open-field test. CBD diminished cortical NF-ĸB activation, IL-6 levels in plasma and brain, and the increased KYN/TRP and KYN/5-HT ratios in hippocampus and cortex in the LPS model. Our results demonstrate that CBD produced antidepressant-like effects in the LPS neuroinflammatory model, associated to a reduction in the kynurenine pathway activation, IL-6 levels and NF-ĸB activation. As CBD stands out as a promising antidepressant drug, more research is needed to completely understand its mechanisms of action in depression linked to inflammation.

Study CAMBIMED: Effects of changes in medication appearance on safety of antihypertensive and hypolipidemic treatments in chronic patients older than 65 years in primary health care.

BACKGROUND: Different studies have investigated the effects that changes in drug appearance have on the control of chronic diseases and drug safety. The main objective of the proposed study is to evaluate if changes in the appearance of the packaging and presentation of drugs having the same active ingredient are related to a decrease in adherence and an increase in usage errors for chronic treatment using antihypertensive (enalapril and amlodipine) and hypolipidemic agents (simvastatin) in patients ≥65 years old, over a one-year follow-up period. METHODS/DESIGN: We propose a multicentric observational longitudinal cohort study with a one-year follow-up period in 8 primary health care centers (PHCC) in the Community of Madrid. 259 patients who are ≥65 years old, hypertensive and/or dyslipidemic, undergoing treatment with enalapril and/or amlodipine and/or simvastatin, and under formal follow-up of chronic patients in primary health care will be selected by simple random sampling. The main outcome variable will be a final combined variable (adherence and medication usage errors). Other included variables will be: sociodemographic and clinical variables of the patient, degree of disease control, drug taken, number of changes in the appearance of each drug by the pharmacy, and the type and frequency of both avoidable and non-avoidable adverse effects during the follow-up period. A descriptive and a multivariate analysis of the variables will be carried out by means of a logistic regression model, using the final combined variable as the dependent variable (error and/or inadequate usage of the drug), and variables shown to be related to it during the bivariate analysis as the independent variables. DISCUSSION: For drugs of the same active ingredient, the effect that different package appearances and presentation may have on the safety of patients undergoing chronic treatments is unknown under the new legislative framework. There are various initiatives that promote the iso-appearance of drugs: "If they are the same, make them look the same". It is to be expected that older, multi-medicated patients with chronic pathologies will be the ones under a greater risk of suffering from this problem.

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.