High PEEP with recruitment maneuvers versus Low PEEP During General Anesthesia for Surgery - a Bayesian individual patient data meta-analysis of three randomized clinical trials.

BACKGROUND: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. METHODS: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. RESULTS: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. CONCLUSION: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.

Sex-dependent effect of socioeconomic status on cardiovascular event risk in a population-based cohort of patients with type 2 diabetes.

BACKGROUND: Socioeconomic status (SES) factors often result in profound health inequalities among populations, and their impact may differ between sexes. The aim of this study was to estimate and compare the effect of socioeconomic status indicators on incident cardiovascular disease (CVD)-related events among males and females with type 2 diabetes (T2D). METHODS: A population-based cohort from a southern European region including 24,650 patients with T2D was followed for five years. The sex-specific associations between SES indicators and the first occurring CVD event were modeled using multivariate Fine-Gray competing risk models. Coronary Heart Disease (CHD) and stroke were considered secondary outcomes. RESULTS: Patients without a formal education had a significantly higher risk of CVD than those with a high school or university education, with adjusted hazard ratios (HRs) equal to 1.24 (95%CI: 1.09-1.41) for males and 1.50 (95%CI: 1.09-2.06) for females. Patients with <18 000€ income had also higher CVD risk than those with ≥18 000€, with HRs equal to 1.44 (95%CI: 1.29-1.59) for males and 1.42 (95%CI: 1.26-1.60) for females. Being immigrant showed a HR equal to 0.81 (95%CI: 0.66-0.99) for males and 1.13 (95%CI: 0.68-1.87) for females. Similar results were observed for stroke, but differed for CHD when income is used, which had higher effect in females. CONCLUSION: Socioeconomic inequalities in CVD outcomes are present among T2D patients, and their magnitude for educational attainment is sex-dependent, being higher in females, suggesting the need to consider them when designing tailored primary prevention and management strategies.

Small area variations in non-affective first-episode psychosis: the role of socioeconomic and environmental factors.

BACKGROUND: There is strong evidence supporting the association between environmental factors and increased risk of non-affective psychotic disorders. However, the use of sound statistical methods to account for spatial variations associated with environmental risk factors, such as urbanicity, migration, or deprivation, is scarce in the literature. METHODS: We studied the geographical distribution of non-affective first-episode psychosis (NA-FEP) in a northern region of Spain (Navarra) during a 54-month period considering area-level socioeconomic indicators as putative explanatory variables. We used several Bayesian hierarchical Poisson models to smooth the standardized incidence ratios (SIR). We included neighborhood-level variables in the spatial models as covariates. RESULTS: We identified 430 NA-FEP cases over a 54-month period for a population at risk of 365,213 inhabitants per year. NA-FEP incidence risks showed spatial patterning and a significant ecological association with the migrant population, unemployment, and consumption of anxiolytics and antidepressants. The high-risk areas corresponded mostly to peripheral urban regions; very few basic health sectors of rural areas emerged as high-risk areas in the spatial models with covariates. DISCUSSION: Increased rates of unemployment, the migrant population, and consumption of anxiolytics and antidepressants showed significant associations linked to the spatial-geographic incidence of NA-FEP. These results may allow targeting geographical areas to provide preventive interventions that potentially address modifiable environmental risk factors for NA-FEP. Further investigation is needed to understand the mechanisms underlying the associations between environmental risk factors and the incidence of NA-FEP.

COVID-19 infection and complications according to ABO blood group in the elderly: A population-based subcohort and meta-analysis.

BACKGROUND AND OBJECTIVES: It is reported that ABO antibodies have a role in COVID-19 infection and severity; however, ABO antibody titres vary with advanced age. The aim was to analyse the association between ABO blood group and risk of COVID-19 infection and complications in elderly patients, and to contrast this data with findings in the overall adult population. MATERIALS AND METHODS: A prospective cohort study of the Navarre (Spain) population aged ≥60 years and a meta-analysis of published studies including participants of ≥60 years were carried out. RESULTS: In the Navarre elderly population, a higher risk of COVID-19 infection was identified in the A versus non-A and O group and lower risk in O versus non-O, with no significant association between hospitalization, intensive care unit admission or mortality and any of the blood groups, results that coincide with those of the overall Navarre adult population. The meta-analyses using studies that included participants of ≥60 years demonstrated a higher risk of hospitalization and mortality in A versus non-A and a lower mortality risk with B versus non-B. Similar mortality results were found in the meta-analyses of the overall adult population. CONCLUSION: There are no relevant differences between the overall adult population and population aged ≥60 years in the risk of COVID-19 infection and severity according to ABO blood groups, suggesting that age-related changes in ABO would be of limited clinical significance.

Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials.

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Role of the AB0 blood group in COVID-19 infection and complications: A population-based study.

Since the beginning of the COVID-19 pandemic, the ABO blood group has been described as a possible biological marker of susceptibility for the disease. This study evaluates the role of ABO group on the risk of SARS-CoV-2 infection and related complications in a population-based cohort including 87,090 subjects from the Navarre population (Northern Spain) with no history of SARS-CoV-2 infection and with known ABO blood group, after one year of the pandemic (May 2020 - May 2021). The risk of infection, hospitalization, Intensive Care Unit (ICU) admission and death was analyzed using multivariate logistic regression, adjusting for possible confounding variables. A lower risk of infection was observed in group 0 vs non-0 groups [OR 0.94 (95 %CI 0.90-0.99)], a higher risk of infection in group A vs non-A groups [OR 1.09 (95 %CI 1.04-1.15)] and a higher risk of infection in group A vs group 0 [OR 1.08 (95CI 1.03-1.14)] (when the 4 groups are analyzed separately). No association was observed between blood groups and hospitalization, ICU admission, or death in SARS-CoV-2 infected subjects. Regarding the risk of SARS-CoV-2 infection, we observed a protective role of group O and a greater risk in the A group.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Effect of a multicomponent exercise program and cognitive stimulation (VIVIFRAIL-COGN) on falls in frail community older persons with high risk of falls: study protocol for a randomized multicenter control trial.

BACKGROUND: Falls represent important drivers of intrinsic capacity losses, functional limitations and reduced quality of life in the growing older adult's population, especially among those presenting with frailty. Despite exercise- and cognitive training-based interventions have shown effectiveness for reducing fall rates, evidence around their putative cumulative effects on falls and fall-related complications (such as fractures, reduced quality of life and functional limitations) in frail individuals remains scarce. The main aim of this study is to explore the effectiveness program combining an individualized exercise program and an executive function-based cognitive training (VIVIFRAIL-COGN) compared to usual care in the prevention of falls and fall-related outcomes over a 1-year follow-up. METHODS: This study is designed as a four-center randomized clinical trial with a 12-week intervention period and an additional 1-year follow-up. Three hundred twenty frail or pre-frail (≥ 1 criteria of the Frailty Phenotype) older adults (≥ 75 years) with high risk of falling (defined by fall history and gait performance) will be recruited in the Falls Units of the participating centers. They will be randomized in a 1:1 ratio to the intervention group (IG) or the control group (CG). The IG will participate in a home-based intervention combining the individualized Vivifrail multicomponent (aerobic, resistance, gait and balance and flexibility) exercise program and a personalized executive function-based cognitive training (VIVIFRAIL-COGN). The CG group will receive usual care delivered in the Falls Units, including the Otago Exercise Program. Primary outcome will be the incidence of falls (event rate/year) and will be ascertained by self-report during three visits (at baseline, and 6 and 12 weeks) and telephone-based contacts at 6, 9 and 12 months after randomization. Secondarily, effects on measures of physical and cognitive function, quality of life, nutritional, muscle quality and psychological status will be evaluated. DISCUSSION: This trial will provide new evidence about the effectiveness of an individualized multidomain intervention by studying the effect of additive effects of cognitive training and physical exercise to prevent falls in older frail persons with high risk of falling. Compared to usual care, the combined intervention is expected to show additive effects in the reduction of the incidence of falls and associated adverse outcomes. TRIAL REGISTRATION: NCT04911179 02/06/2021.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV).

OBJECTIVE: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. DESIGN: International, multicenter, prospective, randomized controlled clinical trial. SETTING: A network of university hospitals. PARTICIPANTS: The study comprises 1,380 patients scheduled for thoracic surgery. INTERVENTIONS: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. MEASUREMENTS AND MAIN RESULTS: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients.

Socioeconomic inequalities in cardiometabolic control in patients with type 2 diabetes.

BACKGROUND: The aim of this study was to determine if the achievement of control targets in patients with type 2 diabetes was associated with personal socioeconomic factors and if these associations were sex-dependent. METHODS: This cross-sectional, population-based study was conducted in Spain. Glycated haemoglobin (HbA1c) level and other clinical parameters were obtained from electronic primary care records (n = 32,638 cases). Socioeconomic status was determined using education level and yearly income. Among patients, having their HbA1c level checked during the previous year was considered as an indirect measure of the process of care, whereas tobacco use and clinical parameters such as HbA1c, low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) were considered intermediate control outcomes. General linear mixed effect models were used to assess associations. RESULTS: The achievement of metabolic and cardiovascular control targets in patients with type 2 diabetes was associated with educational level and income, and socioeconomic gradients differed by sex. The probability of having had an HbA1c test performed in the previous year was higher in patients with lower education levels. Patients in the lowest income and education level categories were less likely to have reached the recommended HbA1c level. Males in the lowest education level categories were less likely to be non-smokers or to have achieved the blood pressure targets. In contrast, patients within the low income categories had a higher probability of reaching the recommended LDL-c level. CONCLUSIONS: Our results suggest the presence of socioeconomic inequalities in the achievement of cardiovascular and metabolic control that differed in direction and magnitude depending on the measured outcome and sex of the patient. These findings may help health professionals focus on high-risk individuals to decrease health inequalities.

Trends and area variations in Potentially Preventable Admissions for COPD in Spain (2002-2013): a significant decline and convergence between areas.

BACKGROUND: Potentially Preventable Hospitalizations (PPH) are hospital admissions for conditions which are preventable with timely and appropriate outpatient care being Chronic Obstructive Pulmonary Disease (COPD) admissions one of the most relevant PPH. We estimate the population age-sex standardized relative risk of admission for COPD-PPH by year and area of residence in the Spanish National Health System (sNHS) during the period 2002-2013. METHODS: The study was conducted in the 203 Hospital Service Areas of the sNHS, using the 2002 to 2013 hospital admissions for a COPD-PPH condition of patients aged 20 and over. We use conventional small area variation statistics and a Bayesian hierarchical approach to model the different risk structures of dependence in both space and time. RESULTS: COPD-PPH admissions declined from 24.5 to 15.5 per 10,000 persons-year (Men: from 40.6 to 25.1; Women: from 9.1 to 6.4). The relative risk declined from 1.19 (19 % above 2002-2013 average) in 2002 to 0.77 (30 % below average) in 2013. Both the starting point and the slope were different for the different regions. Variation among admission rates between extreme areas dropped from 6.7 times higher in 2002 to 4.6 times higher in 2013. CONCLUSIONS: COPD-PPH conditions in Spain have undergone a strong decline and a reduction in geographical variation in the last 12 years, suggesting a general improvement in health policies and health care over time. Variability among areas still remains, with a substantial room for improvement.

Joint spatial modeling to identify shared patterns among chronic related potentially preventable hospitalizations.

BACKGROUND: Rates of Potentially Preventable Hospitalizations (PPH) are used to evaluate access of territorially delimited populations to high quality ambulatory care. A common geographic pattern of several PPH would reflect the performance of healthcare providers. This study is aimed at modeling jointly the geographical variation in six chronic PPH conditions in one Spanish Autonomous Community for describing common and discrepant patterns, and to assess the relative weight of the common pattern on each condition. METHODS: Data on the 39,970 PPH hospital admissions for diabetes short term complications, chronic obstructive pulmonary disease (COPD), congestive heart failure, dehydration, angina admission and adult asthma, between 2007 and 2009 were extracted from the Hospital Discharge Administrative Databases and assigned to one of the 240 Basic Health Zones. Rates and Standardized Hospitalization Ratios per geographic unit were estimated. The spatial analysis was carried out jointly for PPH conditions using Shared Component Models (SCM). RESULTS: The component shared by the six PPH conditions explained about the 36% of the variability of each PPH condition, ranging from the 25.9 for dehydration to 58.7 for COPD. The geographical pattern found in the latent common component identifies territorial clusters with particularly high risk. The specific risk pattern that each isolated PPH does not share with the common pattern for all six conditions show many non-significant areas for most PPH, but with some exceptions. CONCLUSIONS: The geographical distribution of the risk of the PPH conditions is captured in a 36% by a unique latent pattern. The SCM modeling may be useful to evaluate healthcare system performance.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver transplantation.

OBJECTIVE: A meta-analysis was carried out of published studies on the effect of the CYP3A5 6986A>G polymorphism in liver donors and transplant recipients on tacrolimus pharmacokinetics. METHODS: Cohort studies that evaluated the relationship between the CYP3A5 polymorphism in liver donors and transplant recipients and tacrolimus, trough blood concentration normalized for the daily dose (C) per kilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to 1 year after transplantation, were included. Data were not restricted by patient age or the language or journal of publication. A literature search was conducted using the Cochrane Library, MEDLINE, EMBASE, and grey literature, and articles published up to 24 April 2013 were selected. Data were pooled (random-effects model), and the results were expressed as the mean difference of the corresponding C/D ratios and 95% confidence intervals. RESULTS: Six studies involving donor genotypes (254 patients) and four involving recipient genotypes (180 patients) were ultimately included. The meta-analysis showed the C/D ratio to be significantly higher in recipients with nonexpresser donor variants at all time points. In recipients, the variant did not influence the C/D ratio. CONCLUSION: The presence of the CYP3A5 6986A>G polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although only the evidence available for the first month after transplantation was of adequate quality for demonstrating a significant difference. The evidence provided here shows no effect of the recipient genotype; however, the quality of the evidence was low, thereby precluding the drawing of firm conclusions.

Multimodal Prehabilitation in Heart Transplant Recipients Improves Short-Term Post-Transplant Outcomes without Increasing Costs.

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

Timing of surgery for hip fracture and in-hospital mortality: a retrospective population-based cohort study in the Spanish National Health System.

BACKGROUND: While the benefits or otherwise of early hip fracture repair is a long-running controversy with studies showing contradictory results, this practice is being adopted as a quality indicator in several health care organizations. The aim of this study is to analyze the association between early hip fracture repair and in-hospital mortality in elderly people attending public hospitals in the Spanish National Health System and, additionally, to explore factors associated with the decision to perform early hip fracture repair. METHODS: A cohort of 56,500 patients of 60-years-old and over, hospitalized for hip fracture during the period 2002 to 2005 in all the public hospitals in 8 Spanish regions, were followed up using administrative databases to identify the time to surgical repair and in-hospital mortality. We used a multivariate logistic regression model to analyze the relationship between the timing of surgery (< 2 days from admission) and in-hospital mortality, controlling for several confounding factors. RESULTS: Early surgery was performed on 25% of the patients. In the unadjusted analysis early surgery showed an absolute difference in risk of mortality of 0.57 (from 4.42% to 3.85%). However, patients undergoing delayed surgery were older and had higher comorbidity and severity of illness. Timeliness for surgery was not found to be related to in-hospital mortality once confounding factors such as age, sex, chronic comorbidities as well as the severity of illness were controlled for in the multivariate analysis. CONCLUSIONS: Older age, male gender, higher chronic comorbidity and higher severity measured by the Risk Mortality Index were associated with higher mortality, but the time to surgery was not.

Cardiovascular risk in patients with type 2 diabetes: A systematic review of prediction models.

AIMS: To identify all cardiovascular disease risk prediction models developed in patients with type 2 diabetes or in the general population with diabetes as a covariate updating previous studies, describing model performance and analysing both their risk of bias and their applicability METHODS: A systematic search for predictive models of cardiovascular risk was performed in PubMed. The CHARMS and PROBAST guidelines for data extraction and for the assessment of risk of bias and applicability were followed. Google Scholar citations of the selected articles were reviewed to identify studies that conducted external validations. RESULTS: The titles of 10,556 references were extracted to ultimately identify 19 studies with models developed in a population with diabetes and 46 studies in the general population. Within models developed in a population with diabetes, only six were classified as having a low risk of bias, 17 had a favourable assessment of applicability, 11 reported complete model information, and also 11 were externally validated. CONCLUSIONS: There exists an overabundance of cardiovascular risk prediction models applicable to patients with diabetes, but many have a high risk of bias due to methodological shortcomings and independent validations are scarce. We recommend following the existing guidelines to facilitate their applicability.