Which information derived from the Coma Recovery Scale-Revised provides the most reliable prediction of clinical diagnosis and recovery of consciousness? A comparative study using machine learning techniques.

BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) is the most recommended clinical tool to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. AIM: This study investigates which information derived from the CRS-R provides the most reliable prediction of both the clinical diagnosis and recovery of consciousness at the discharge of a long-term neurorehabilitation program. DESIGN: Retrospective observational multisite study. SETTING: The enrollment was performed in three neurorehabilitation facilities of the same hospital network. POPULATION: A total of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were enrolled. METHODS: Machine learning classifiers were trained to predict the clinical diagnosis and recovery of consciousness at discharge using clinical confounders and different metrics extracted from the CRS-R scale. RESULTS: Results showed that the neurobehavioral state at discharge was predicted with acceptable and comparable predictive value with all the indices and measures derived from the CRS-R, but for the clinical diagnosis and the Consciousness Domain Index, and the recovery of consciousness was predicted with higher accuracy and similarly by all the investigated measures, with the exception of initial clinical diagnosis. CONCLUSIONS: Interestingly, the total score in the CRS-R and, especially, the total score in its subscales provided the best overall results, in contrast to the clinical diagnosis, which could indicate that a comprehensive measure of the clinical diagnosis rather than the condition of the individuals could provide a more reliable prediction of the neurobehavioral progress of individuals with prolonged DOC. CLINICAL REHABILITATION IMPACT: The results of this work have important implications in clinical practice, offering a more accurate prognosis of patients and thus giving the possibility to personalize and optimize the rehabilitation plan of patients with DoC using low-cost and easily collectable information.

Spanish COPD Guideline (GesEPOC) Update: Comorbidities, Self-Management and Palliative Care. / Actualización de la Guía Española de la EPOC (GesEPOC): comorbilidades, automanejo y cuidados paliativos.

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD.

Administration of mycophenolic acid is not associated with malformations in descendants from kidney transplanted males.

BACKGROUND: In pregnant women, the use of Mycophenolic acid (MPA) is associated with teratogenicity. Recently, the European Medicines Agency (EMEA) and the Spanish Agency of Medicine and Sanitary Products (AEMPS) warned about the potential teratogenic effects of MPA. These adverse events may occur even in children from males on treatment with MPA. However, evidence of malformations in offsprings of male kidney transplanted patients (KT) exposed to MPA is limited. Thus, the present study aimed to evaluate the incidence of offspring malformations in children of renal transplanted males under MPA. MATERIALS AND METHODS: We conducted a retrospective study in which we evaluated the incidence of malformations in descendants from male recipients that were exposed or not to MPA before and at the time of conception. Two groups of patients were evaluated. Those exposed to MPA (MPA group, n = 20) and the non-MPA group (n = 13) that included patients that did not receive AZA (n = 5) and eight that did receive AZA (n = 8) at the time of conception. RESULTS: A total of forty-nine post-transplant conceptions were identified from 33 different renal transplanted males. MPA was used as the immunosuppressant in 28 of the conceptions. Males from the non-MPA group fathered the other 21 children. Median time from grafting to conception was 6.1 (IQR 2.4-11.1) years, and it was similar between groups. There were eight miscarriage episodes, 2 in the non-MPA group and 6 in the MPA group although differences were not reached. After that, all patients had children without problems. No malformations were detected in any of the 49 regardless whether they were exposed or not to MPA. CONCLUSIONS: No evidence of MPA-associated malformations was observed in descendants of kidney transplanted males on treatment with MPA. Further research is warranted to confirm our findings to properly advice transplanted males keen to procreate.

Retract p < 0.005 and propose using JASP, instead.

Seeking to address the lack of research reproducibility in science, including psychology and the life sciences, a pragmatic solution has been raised recently:  to use a stricter p < 0.005 standard for statistical significance when claiming evidence of new discoveries. Notwithstanding its potential impact, the proposal has motivated a large mass of authors to dispute it from different philosophical and methodological angles. This article reflects on the original argument and the consequent counterarguments, and concludes with a simpler and better-suited alternative that the authors of the proposal knew about and, perhaps, should have made from their Jeffresian perspective: to use a Bayes factors analysis in parallel (e.g., via JASP) in order to learn more about frequentist error statistics and about Bayesian prior and posterior beliefs without having to mix inconsistent research philosophies.

Behavioral recovery in disorders of consciousness: a prospective study with the Spanish version of the Coma Recovery Scale-Revised.

OBJECTIVE: To describe the clinical characteristics and short-term pattern of evolution of a sample of patients within 1 year after acquiring a brain injury that led to a vegetative state (VS) or a minimally conscious state (MCS). DESIGN: Cohort study. SETTING: Inpatient brain injury rehabilitation program. PARTICIPANTS: Patients with acquired brain injury (N=32; 47% traumatic, 37.5% hemorrhagic, 15.5% anoxic) who were in a VS or an MCS according to Coma Recovery Scale-Revised (CRS-R) scores. INTERVENTION: Integrative multisensory program comprising daily physical rehabilitation procedures and multimodal sensory stimulation. MAIN OUTCOME MEASURE: All patients were assessed with a Spanish version of the CRS-R at admission and then monthly for at least 6 months or until emergence from MCS. RESULTS: At the time of admission, 12 patients were diagnosed as being in a VS and 20 as being in an MCS. Eight patients were able to emerge from their MCS during follow-up. Seven of these 8 patients were diagnosed as being in an MCS at inclusion, and only 1 was diagnosed as being in a VS. Emergence from an MCS was mostly associated with improvement in both the communication and motor function scales (n=4). Lesser chronicity (P=.01) and the presence of more than visual behavioral responses at admission (P=.05) were both significant predictors of emergence from an MCS. CONCLUSIONS: The CRS-R seems appropriate for establishing an immediate prognosis in this population. A quick referral of these patients for specialized assessment and rehabilitation facilities is recommended.

[Outpatient monitoring of oesophageal pH with a catheter-free pH-meter (Bravo System). A Study of tolerance, safety and efficacy]. / Monitorización ambulatoria del pH esofágico con pH-metría sin sonda (sistema Bravo(R)). Estudio de tolerancia, seguridad y eficacia.

BACKGROUND AND OBJECTIVE: A new catheter-free outpatient oesophageal pH-meter system (Bravo) has recently been developed. The objective of this study is to test the tolerance, safety and efficacy of the system in the measurement of gastric-oesophageal reflux by comparing it with a conventional pH system. PATIENTS AND METHOD: The study was performed on a control group consisting of 10 healthy volunteers (group 1) and in a group of 40 patients with symptoms of gastric-oesophageal reflux disease (groups 2 and 3). An upper digestive system endoscopy, oesophageal manometry and oesophageal pH measurements with a conventional system and/or with the Bravo catheter-free system, was performed on all patients. All patients who had both tests done (groups 1 and 2) filled in a questionnaire on any physical problems and changes in their daily activity. RESULTS: The test tolerance was higher with the Bravo system in the 9 parameters studied. In the group of healthy volunteers (group 1), the median (range) of the total percentage of pH < 4 was 1.1% (0.5-3.1) with the conventional pH and 1.7% (0-3.4) with the Bravo. When comparing the patients with symptoms of gastric-oesophageal reflux disease (group 2) with those who had only one type of pH measurement made, the acid reflux was significantly higher in patients with Barrett's oesophagus than in the rest of the groups, with conventional pH as well as with the Bravo. If we analyse the patient group with disease due to gastric-oesophageal reflux with those on whom both techniques were used (group 3), 7 of the 10 patients had a pathological reflux that only showed up on measuring pH with the Bravo system. CONCLUSIONS: Catheter-free pH measurements (Bravo) is better tolerated and with better satisfaction for the healthy volunteers and patients than with conventional PH, even, on occasions being more efficient for studying acid reflux due to the lower incidence of negative results.

Value of serological testing for diagnosis of legionellosis in outbreak patients.

Serum antibody detection tests and a urine antigen detection technique were compared in samples from 116 patients epidemiologically characterized as belonging to a legionellosis outbreak. Sera were tested by enzyme-linked immunosorbent assays (ELISAs) for immunoglobulin M (IgM) and IgG plus IgM and by immunofluorescent assays (IFAs) for IgG, IgM, IgA, and polyimmunoglobulin using commercial kits (Vircell); concentrated urines were tested with the Binax NOW Legionella test. ELISA for IgM, ELISA for IgG plus IgM, antigenuria detection, and IFA for IgM were able to diagnose 72.3%, 60.5%, 53.3%, and 51.4%, respectively, of patients. Antigenuria was present in 53.8% of first samples, ELISA detected IgM in 29.7%, ELISA detected IgG plus IgM in 7.9%, and IFA detected IgM in 3.9%. Ten antigenuria-negative first samples tested serologically positive, 9 of them to IgM by ELISA. Despite the single source of the samples included in the study, detection of IgM using a sensitive technique such as ELISA seems to be a suitable complement to antigenuria detection for the diagnosis of legionellosis.

Pharmacokinetics of ciprofloxacin as a tool to optimise dosage schedules in community patients.

OBJECTIVE: To evaluate the dosage regimens of ciprofloxacin prescribed for outpatients by applying the principles of antibacterial therapy. DESIGN: Retrospective analysis of prescription and demographic data. SETTING: Community pharmacy in Valladolid, Spain. PATIENTS: Fifty male and female patients aged 18-93 years and with bodyweight 41-95kg. METHODS: Prescribed dosage regimen, age, weight, height, type of infection, comorbidity and coadministered drugs were recorded for each patient. Plasma concentration curves were simulated from literature values of the pharmacokinetic parameters of the drug and the age and weight of the patients. Urine concentrations were estimated from simulated plasma concentrations, literature values of renal clearance and an average urinary flow rate of 2 L/day. The potential efficacy of the prescribed treatment was evaluated from the ratio of the simulated peak plasma concentration (C(max)) to the literature value of the minimum inhibitory concentration (MIC) for the bacterium most probably responsible for the infection (C(max) /MIC). The ratio of area under the plasma concentration-time curve over 24 hours to MIC (AUC24 /MIC) was also estimated for non-urinary infections. RESULTS: Demographic variables such as age or bodyweight do not seem to be taken in consideration when ciprofloxacin is prescribed, at least in the patients considered here, leading to wide interindividual variability in plasma concentrations. This may not be relevant for urinary infections, since ciprofloxacin concentrates in the urine, leading to high Cmax /MIC ratios in all patients. Simulated plasma concentration-time curves revealed consistent underdosing for systemic infections in young patients over 60kg, for whom the plasma concentrations achieved led to Cmax /MIC and AUC24 /MIC ratios lower than those associated with clinical efficacy and minimal spread of bacterial resistance. CONCLUSIONS: The standard regimen of ciprofloxacin 250mg every 12 hours prescribed for urinary infections may not be the best choice, since a more convenient regimen of 500mg once daily leads to a higher Cmax /MIC ratio, which is associated with a more significant postantibiotic effect and higher efficacy of fluoroquinolones. For non-urinary infections, the age and weight of patients should be taken into account to achieve optimum plasma concentrations.

Pharmacokinetic/pharmacodynamic modelling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections.

A simulation study was performed to evaluate and compare the standard dosage regimen of 250 mg/12 h versus 500 mg/24 h of ciprofloxacin for the treatment of urinary tract infections (UTIs). Pharmacokinetic parameters reported for healthy young and old individuals were used for the simulation of drug levels in urine, at different mean urine flow rates (1-2.5 L/day). Pharmacokinetic/pharmacodynamic analysis of the results revealed that 500 mg ciprofloxacin once a day produced a more favourable profile in urine than 250 mg/12 h, particularly in the elderly, due to the slower elimination of the drug in this group of patients. Circadian rhythms were also considered for the simulation of drug levels in urine. According to the results, 500 mg once a day administered in the morning would be a better choice than 250 mg/12 h at least for uncomplicated UTI; nevertheless, clinical assays are needed to prove this hypothesis.