Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

A biological condition gradient for Caribbean coral reefs: Part II. Numeric rules using sessile benthic organisms.

The Biological Condition Gradient (BCG) is a conceptual model used to describe incremental changes in biological condition along a gradient of increasing anthropogenic stress. As coral reefs collapse globally, scientists and managers are focused on how to sustain the crucial structure and functions, and the benefits that healthy coral reef ecosystems provide for many economies and societies. We developed a numeric (quantitative) BGC model for the coral reefs of Puerto Rico and the US Virgin Islands to transparently facilitate ecologically meaningful management decisions regarding these fragile resources. Here, reef conditions range from natural, undisturbed conditions to severely altered or degraded conditions. Numeric decision rules were developed by an expert panel for scleractinian corals and other benthic assemblages using multiple attributes to apply in shallow-water tropical fore reefs with depths <30 m. The numeric model employed decision rules based on metrics (e.g., % live coral cover, coral species richness, pollution-sensitive coral species, unproductive and sediment substrates, % cover by Orbicella spp.) used to assess coral reef condition. Model confirmation showed the numeric BCG model predicted the panel's median site ratings for 84% of the sites used to calibrate the model and 89% of independent validation sites. The numeric BCG model is suitable for adaptive management applications and supports bioassessment and criteria development. It is a robust assessment tool that could be used to establish ecosystem condition that would aid resource managers in evaluating and communicating current or changing conditions, protect water and habitat quality in areas of high biological integrity, or develop restoration goals with stakeholders and other public beneficiaries.

A biological condition gradient for coral reefs in the US Caribbean Territories: Part I. Coral narrative rules.

As coral reef condition and sustainability continue to decline worldwide, losses of critical habitat and their ecosystem services have generated an urgency to understand and communicate reef response to management actions, environmental contamination, and natural disasters. Increasingly, coral reef protection and restoration programs emphasize the need for robust assessment tools for protecting high-quality waters and establishing conservation goals. Of equal importance is the need to communicate assessment results to stakeholders, beneficiaries, and the public so that environmental consequences of decisions are understood. The Biological Condition (BCG) model provides a structure to evaluate the condition of a coral reef in increments of change along a gradient of human disturbance. Communication of incremental change, regardless of direction, is important for decision makers and the public to better understand what is gained or lost depending on what actions are taken. We developed a narrative (qualitative) Biological Condition Gradient (BCG) from the consensus of a diverse expert panel to provide a framework for coral reefs in US Caribbean Territories. The model uses narrative descriptions of biological attributes for benthic organisms to evaluate reefs relative to undisturbed or minimally disturbed conditions. Using expert elicitation, narrative decision rules were proposed and deliberated to discriminate among six levels of change along a gradient of increasing anthropogenic stress. Narrative rules for each of the BCG levels are presented to facilitate the evaluation of benthic communities in coral reefs and provide specific narrative features to detect changes in coral reef condition and biological integrity. The BCG model can be used in the absence of numeric, or quantitative metrics, to evaluate actions that may encroach on coral reef ecosystems, manage endangered species habitat, and develop and implement management plans for marine protected areas, watersheds, and coastal zones. The narrative BCG model is a defensible model and communication tool that translates scientific results so the nontechnical person can understand and support both regulatory and non-regulatory water quality and natural resource programs.

Statistical Modeling of the Seismic Moments via Mathai Distribution.

Mathai's pathway model is playing an increasingly prominent role in statistical distributions. As a generalization of a great variety of distributions, the pathway model allows the studying of several non-linear dynamics of complex systems. Here, we construct a model, called the Pareto-Mathai distribution, using the fact that the earthquakes' magnitudes of full catalogues are well-modeled by a Mathai distribution. The Pareto-Mathai distribution is used to study artificially induced microseisms in the mining industry. The fitting of a distribution for entire range of magnitudes allow us to calculate the completeness magnitude (Mc). Mathematical properties of the new distribution are studied. In addition, applying this model to data recorded at a Chilean mine, the magnitude Mc is estimated for several mine sectors and also the entire mine.

Efficacy and safety comparative study of dexrabeprazole vs. esomeprazole for the treatment of gastroesophageal reflux disease.

INTRODUCTION: A national survey in the general population showed that gastroesophageal reflux disease (GERD) is highly prevalent in Mexico. OBJECTIVE: To compare the efficacy and safety of two isomers, dexrabeprazole (10 mg) vs. esomeprazole (20 mg), in the treatment of GERD for four weeks. METHODS: Randomized, multicenter, prospective, double-blind phase III clinical trial in two groups that included 230 patients. RESULTS: A statistically significant decrease in the severity of GERD symptoms (heartburn, regurgitation, epigastric pain and dysphagia), evaluated using a visual analogue scale, was observed with both treatments. Mean score for dexrabeprazole on Carlsson-Dent questionnaire at 28 days was 2.12, and for esomeprazole, 3.02. Both treatments were effective, with no statistically significant difference being recorded (p < 0.05). On SF-36 health questionnaire, both were observed to improve the quality-of-life score, with no significant difference being identified. Both drugs were well tolerated, and the adverse event incidence profile was low. CONCLUSIONS: In the treatment of non-erosive GERD, the use of dexrabeprazole at 10 mg/day is as effective as esomeprazole 20 mg/day, with the advantage that the dose is lower with an appropriate safety profile.

INTRODUCCIÓN: Una encuesta nacional en población abierta mostró que la enfermedad por reflujo gastroesofágico (ERGE) tiene alta prevalencia en México. OBJETIVO: Comparar la eficacia y seguridad de dos isómeros, dexrabeprazol (10 mg) versus esomeprazol (20 mg), en el tratamiento de la ERGE durante cuatro semanas. MÉTODOS: Ensayo clínico fase III, aleatorizado, multicéntrico, prospectivo, doble ciego, en dos grupos que incluyeron 230 pacientes. RESULTADOS: Con ambos tratamientos se observó disminución estadísticamente significativa en la severidad de los síntomas de ERGE (pirosis, regurgitación, dolor epigástrico y disfagia), evaluados mediante una escala visual análoga. La puntuación promedio de dexrabeprazol en el Cuestionario de Carlsson-Dent a los 28 días fue de 2.12 y la de esomeprazol de 3.02. Ambos tratamientos fueron efectivos, sin diferencia estadísticamente significativa (p < 0.05). En el Cuestionario de Salud SF-36 se observó que ambos mejoraron la puntuación en la calidad de vida, sin diferencia significativa. Ambos medicamentos fueron bien tolerados y el perfil de incidencia de eventos adversos fue bajo. CONCLUSIONES: En el tratamiento de ERGE no erosiva, el uso de 10 mg/día de dexrabeprazol es tan efectivo como 20 mg/día de esomeprazol, con la ventaja de que la dosis es menor con un adecuado perfil de seguridad.

Clinical and economic impact of current ALK rearrangement testing in Spain compared with a hypothetical no-testing scenario.

BACKGROUND: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. METHODS: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. RESULTS: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. CONCLUSIONS: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain.

[Effects of pharmaceutical counseling on the effectiveness of anticoagulation in patients with atrial fibrillation]. / Impacto de la atención farmacéutica en la calidad del tratamiento con acenocumarol en pacientes con fibrilación auricular.

BACKGROUND: Vitamin K antagonists such as acenocoumarol and warfarin are usually indicated for the treatment of Atrial Fibrillation (AF). The Therapeutic Range Time (TRT) is a quality of treatment indicator. Values greater than 65% are associated with significantly lower stroke and bleeding rates. Proper pharmaceutical care improves TRT. AIM: To evaluate the impact of pharmaceutical care in patients with AF treated with acenocoumarol. MATERIAL AND METHODS: We studied 41 patients using acenocoumarol for AF aged 71 ± 11 years (43% women). They received pharmaceutical counseling during 12 weeks. TRT was calculated retrospectively for the year before counseling and prospectively during the intervention period. RESULTS: After receiving pharmaceutical counseling TRT improved from 29% at baseline to 46% at the end of the intervention (p < 0.01). After pharmaceutical care, the adherence of patients to drug treatment improved from 27% at baseline to 85% at the end of the study. The user satisfaction survey of the pharmaceutical care received showed a high degree of patient satisfaction. CONCLUSIONS: Pharmaceutical care in patients with oral anticoagulant treatment improves TRT of anticoagulation. It is accepted and positively evaluated by patients.

Impact of Hurricanes Irma and Maria on Puerto Rico Maternal and Child Health Research Programs.

Puerto Rico was hit by two major hurricanes in September 2017 causing great devastation, losing over 90% of the power grid, wireless communication and access to potable water, and destroying many homes. Our research programs: Puerto Rico Testsite for Exploring Contamination Threats (PROTECT), Center for Research on Early Childhood Exposure and Development in Puerto Rico (CRECE), Zika in Infants and Pregnancy (ZIP), and Environmental Influences on Child Health Outcomes (ECHO) are ongoing observational cohort studies that have been investigating environmental risk factors for perinatal health outcomes among Puerto Rican mothers and infants. Our projects paused operations for about two weeks, to begin recovery process and become a source of assistance, retaining 95% of study participants across all research programs. We joined with various groups to ensure the safety and welfare of team members, study participants, community health center partners, and members of the surrounding communities. We learned important lessons about the impact of these hurricanes and the difficulties of the recovery. Major challenges post-hurricanes were access to care and nutrition, maternal stress, and environmental damage. We understood the need to integrate disaster preparedness into our programs' operating procedures and future applications, recognizing that these events will recur. We will grow resilience among our staff, maternal and child health partners, and participants by building on the experience of these two storms.

Evolution of a mass spectrometry-grade protease with PTM-directed specificity.

Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This requirement catalyzed our efforts to evolve MS-grade mutant PTM-directed proteases. Citrulline, a PTM implicated in epigenetic and immunological function, made an ideal first target, because citrullination eliminates arginyl tryptic sites. Bead-displayed trypsin mutant genes were translated in droplets, the mutant proteases were challenged to cleave bead-bound fluorogenic probes of citrulline-dependent proteolysis, and the resultant beads (1.3 million) were screened. The most promising mutant efficiently catalyzed citrulline-dependent peptide bond cleavage (kcat/KM = 6.9 × 105 M-1⋅s-1). The resulting C-terminally citrullinated peptides generated characteristic isotopic patterns in MALDI-TOF MS, and both a fragmentation product y1 ion corresponding to citrulline (176.1030 m/z) and diagnostic peak pairs in the extracted ion chromatograms of LC-MS/MS analysis. Using these signatures, we identified citrullination sites in protein arginine deiminase 4 (12 sites) and in fibrinogen (25 sites, two previously unknown). The unique mass spectral features of PTM-dependent proteolytic digest products promise a generalized PTM site-mapping strategy based on a toolbox of such mutant proteases, which are now accessible by laboratory evolution.

Identification of somatic and germ-line DICER1 mutations in pleuropulmonary blastoma, cystic nephroma and rhabdomyosarcoma tumors within a DICER1 syndrome pedigree.

BACKGROUND: DICER1 syndrome is a pediatric cancer predisposition condition causing a variety of tumor types in children and young adults. In this report we studied a family with two relatives presenting a variety of neoplastic conditions at childhood. METHODS: Germ-line mutation screening of the complete coding region of the DICER1 gene in genomic DNA from the proband was performed. The presence of somatic DICER1 mutation and further alterations in driver genes was investigated in genomic DNA obtained from available tumor samples. RESULTS: A nonsense germ-line mutation in DICER1 causing a truncated protein at the IIIb domain level was identified segregating within a family including two affected relatives who developed in one case cystic nephroma and pleuropulmonary blastoma, and rhabdomyosarcoma and multinodular goiter in the other. Additional in trans DICER1 missense somatic mutations in the IIIb DICER1 domain were found both in the cystic nephroma and in the rhabdomyosarcoma, suggesting that neoplasms in this family might arise from the unusual two-hit mechanism for DICER-derived tumorigenesis in which after the presence of a truncated constitutive protein, a neomorphic DICER1 activity is somatically adquired. Additional genetic alterations, such as TP53 mutations, were identified in the rhabdomyosarcoma. CONCLUSIONS: Besides DICER1 loss of standard activity, oncogenic cooperation of other genes, as mutated TP53, may involve developing higher grade tumors within this syndrome. Given the broad clinical spectrum that may arise, genetic counseling and close surveillance must be offered to all family members at risk of DICER1 syndrome.

Sclerosing Polycystic Adenosis of the Parotid Gland: A Systematic Review and Report of 2 New Cases.

PURPOSE: We sought to evaluate clinical-epidemiologic aspects, pathologic characteristics, and treatment of sclerosing polycystic adenosis (SPA) of the parotid gland and to report 2 new cases. MATERIALS AND METHODS: We conducted a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies published in or before June 2016. The inclusion criteria were as follows: final diagnosis of SPA affecting the parotid gland and articles published in Spanish or English. The exclusion criteria were as follows: unclear diagnosis after pathologic analysis and patients affected by other conditions in the major salivary glands. We added 2 new cases. RESULTS: Our review ultimately included 21 articles and 45 cases. The mean patient age was 41 years (range, 7-84 years). The female-to-male ratio was 2:1. In all patients the tumor showed progressive growth. The evolution range was 7 days to 11 years. In 17.7% of cases, the tumor was associated with pain. The average tumor size was 30.3 mm (range, 12-60 mm). Fine needle aspiration biopsy (FNAB) was unable to diagnose 30 cases. Benign tumors comprised 58% of tumors (18), whereas malignancy was present in 25.8% (8). Thirty-five tumors were well circumscribed. There were 8 multinodular or lobed cases. The tumor was described as encapsulated in 1 case, partially encapsulated or pseudo-encapsulated in 16, and not encapsulated in 12. Five cases showed different degrees of degenerative changes, ranging from dysplasia to invasive carcinoma. All cases underwent surgical treatment. Superficial parotidectomy with preservation of the facial nerve was performed in 22 cases (61.1%), total parotidectomy in 8 (22.2%), and tumor enucleation in 6 (16.6%). The mean follow-up period was 51.5 months (range, 5-276 months). Of documented cases, 74.2% had 2 or more years of follow-up. Recurrences occurred in 6 cases (16.6%). CONCLUSIONS: We consider SPA a benign tumor with progressive growth, which is occasionally painful. It occurs around age 40 years and occurs more often in female patients. Fine needle aspiration biopsy does not provide an adequate preoperative diagnosis. Recurrences are infrequent. Follow-up should be customized according to the pathologic findings. Malignant transformation may occur. Superficial parotidectomy with facial nerve preservation is the treatment of choice.

[Epidemiological profile of traumatic brain injury at the Dr. Rafael A. Calderón Guardia Hospital, Neurosurgery Department, during the period from 2007 to 2012]. / Perfil epidemiológico del traumatismo craneoencefálico en el Servicio de Neurocirugía del Hospital Dr. Rafael A. Calderón Guardia durante el período 2007 a 2012.

OBJECTIVE: To determine the epidemiological profile of the patients who suffered traumatic brain injury (TBI) and were treated at the Dr. Rafael A. Calderón Guardia Hospital (HCG) Neurosurgery department, during the period from 2007 to 2012. MATERIAL AND METHODS: An observational, descriptive, retrospective and cross section study was performed on all the patients with TBI and who were admitted to the emergency room of the HCG during the period 2007 to 2012. There were a total of 721 cases, of which 566 records were obtained of patients who had the variables established in this study, excluding those with incomplete or inconsistent information. RESULTS: The present study established the epidemiological profile of the TBI in the population seen during the period 2007 to 2012 at the HCG. It was determined that the male sex made up the majority of the cases were male, with mean age of 46 years. The mortality rate was 12.69% (n=69). Car accidents were the most frequent cause of TBI (n=259 persons) in the age group of 25 to 44 years, followed by falls (n=174). It was observed that the majority were farmers, followed by students, and then construction workers. No chronic illnesses were recorded in 71.6% of the medical charts. No alcohol or other drugs were reported in 74.9% of the cases, while there was evidence of the presence of alcohol recorded in 22.8%. The clinical and laboratory parameters that had statistical significance (P<.05) were GCS equal to less than 8 (P=.035), presence of mydriasis (P=.00), deviation of the LM (P=.006), cranial fracture (P=.04), lack of endotracheal intubation on admission (P=.007), prolonged PT (P=.04), prolonged PTT (P=.025), and MAP<60 (P=.002). The most frequent surgical procedure in the study population was craniotomy with hematoma drainage alone or associated with some other procedure (esquillectomy or monitoring of PIC) (n=298). CONCLUSIONS: There is great difficulty in determining the epidemiology of TBI worldwide, due to the lack of standardisation of the international studies. From the present study, it can be concluded that the population that mainly suffers from this type of lesion are adults under 45 years old, with car accidents being the main cause of these lesions (45.8%) in combination with alcohol consumption. Also, the consequences of such are aggravated when the victims present with chronic diseases such as, systemic arterial hypertension and mellitus diabetes. As regards the post-traumatic indicators directly related to a poor outcome, it was determined that a GCS score equal to or less than 8, a mean blood pressure less than 60, the prolongation of the coagulation times, the presence of mydriasis, and skull fractures, have a direct association with the negative or fatal outcome for the victim.

The effects of chronic restraint on the morphology of ventral CA1 neurons in female Long Evans rats.

Women are more likely than men to develop psychopathology as a result of stress, but there is little research regarding the effects of a stressful condition and its treatment in female non-human animals, perhaps because of inherent hormonal activity. Recent studies have demonstrated that there are structural and functional differences between the dorsal and ventral hippocampus, but the effects of stress on the morphology of CA1 and CA3 neurons have been studied primarily in the dorsal hippocampus. This study assessed the effects of stress induced by restricted movement on the morphology of ventral hippocampal CA1 neurons in male and female rats. Male and female Long Evans (LE) rats were subjected to restraint stress for 6 h every day for 25 days. One group of rats was used to study the dendritic morphology of CA1 ventral hippocampal neurons using the Golgi-Cox stain. A second group of rats was used to analyze learning and memory using the Morris water maze. Stressed female rats exhibited a decrease in the density of basilar dendritic spines, an increase in the number of apical dendritic intersections and deficits in spatial memory. There were no apparent effects of stress on male rats. Our data support previous findings of a dimorphic response to chronic stress and indicate that the ventral hippocampus is not particularly susceptible to the effects of stress.

Daily administration of atorvastatin and simvastatin for one week improves cardiac function in type 1 diabetic rats.

Short-term administration of statins during the perioperative period has been suggested to improve cardiovascular (CV) outcomes in patients undergoing cardiac and vascular surgery. The effectiveness of this therapy, the optimal administration time and the statin best suited to improve cardiac performance under hyperglycemic conditions, however, are unknown. In this study, we compared the effects of 10 mg/kg/day simvastatin (SV), pravastatin (PV) and atorvastatin (AV), on the CV status of fully anesthetized streptozotocin-induced diabetic rats 4 weeks following diabetes induction. At this stage, cardiac function is compromised. The rats were anesthetized to mimic presurgical conditions. Cardiac status was evaluated twice by echocardiography, first 24 h after statin administration, and then after daily statin administration for 1 week. After 24 h of statin administration, CV parameters were not improved. Continued daily administration of SV and AV over a 1-week period, by contrast, significantly improved ejection fraction from 52.20 ± 2.33% before treatment to 64.89 ± 1.12% with AV and to 69.71 ± 2.30% with SV (n = 9, p < 0.05). The cardiac output index was also significantly improved from 51.13 ± 6.86 ml/min × 100 g body weight (BW) before treatment to 98.74 ± 13.78 ml/min × 100 g BW with AV and to 84.94 ± 8.64 ml/min × 100 g BW with SV. Only AV increased stroke volume from 0.50 ± 0.08 to 0.83 ± 0.13 ml (n = 9, p < 0.05). Unlike the other statins tested, PV provided no beneficial effects, regardless of the regimen of administration. Our results indicate that daily administration of AV and SV for 1 week enhances cardiac performance in fully anesthetized diabetic rats. This study of short-term statin administration may have strong clinical implications for improving perioperative outcomes in diabetic patients.

Neonatal olfactory bulbectomy causes dendritic spine retraction in dorsal hippocampal CA3 neurons in female rats and spatial learning deficits in male rats.

Olfactory bulbectomy (OBX) is an experimental strategy that is widely employed because it produces changes at different levels (from behavioral to molecular) that can be related to symptoms of depression in humans. This procedure has been widely studied in adult rats, but little information has been obtained of its effect in neonatal rats. The objective of the present study was to evaluate learning and memory capacity and dendritic spine density in dorsal hippocampal CA3 neurons. Seven-day-old male and female Wistar rats were subjected to nOBX by suction, we included an intact group as a control (CON) and a sham-operated group (SHAM), too. Spatial learning and memory were measured at 56 days of age using a Morris water maze. A different cohort of experimental groups was used to measure dendritic spine density by Golgi-Cox impregnation. Male rats with nOBX showed a pronounced spatial learning deficit than female rats. Also, there was a significant decrease in basilar dendritic spine density in female rats with nOBX compared to the CON group. No changes were observed in this variable in male rats with nOBX. Our results allow us to suggest that there is sexual dimorphism in the effect of nOBX on the dorsal hippocampus and its relationship with spatial learning and memory processes.

Acute Respiratory Failure Secondary to Low-Dose Opioid Administration in a Patient With Obstructive Sleep Apnea and Obesity Hypoventilation Syndrome After Undergoing Trans-sphenoidal Tumor Resection.

We present a case of an obese 56-year-old male with obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), and pituitary macroadenoma, who underwent nasal endoscopic trans-sphenoidal resection. Surgery was performed under general anesthesia, uneventfully as planned. The patient experienced, however, delayed emergence despite receiving adequate neuromuscular blockade agent reversal. Extubation was performed and the patient was transferred to the recovery room on a Venturi mask (50% fraction of inspired oxygen, FIO2)and 93% saturation. Postoperatively, the patient was complaining of acute pain that did not resolve with non-opioid medications and a low morphine dose (0.035 mg/kg) for pain management was administered. Subsequently, he developed severe respiratory depression, requiring intubation. After three hours, the patient was extubated, transferred to the intensive care unit, and discharged five days later. Although the patient recovered favorably, this case highlights the risks of administering opioids to patients with OSA and OHS. To our knowledge, this is the first case reporting extreme respiratory depression secondary to the administration of a very low dose of morphine in patients with these comorbidities. Therefore, it is essential to be cautious with the use of opioids and to explore multimodal pain relief methods for these patients.

Clinical dashboard development and implementation to standardize data capture and reporting across health-system specialty pharmacies.

PURPOSE: To describe the development and implementation of clinical dashboards to standardize data capturing and reporting across multiple partner health systems. SUMMARY: Between July and September 2020, clinical dashboards were developed and implemented across multiple partner health-system specialty pharmacies (HSSPs) located throughout the United States. The dashboards were developed via collaboration between personnel involved in clinical subcommittees, clinical outcomes, data analytics, information technology, and clinical and central operations. Utilizing a cloud-scale business intelligence service, patient clinical data documented in a shared patient management system was utilized to create customizable dashboards that displayed patient-reported outcome measures, collected laboratory or test results, and completed pharmacist interventions. Separate dashboards were developed for several disease states and/or medication classes. Based on specialty pharmacy recommendations, medical literature, and clinical guidelines, internally developed disease-specific protocols defined data included in the dashboards and ensured consistent data collection amongst partner health systems. Having access to real-time clinical information allows health systems to closely monitor performance metrics, track patient outcomes, and identify operational gaps. CONCLUSION: Accurately capturing and reporting clinical metrics using clinical dashboards can assist HSSPs in delivering high-quality care. Having access to clinical outcome measures allows HSSPs to better understand the impact of their services on patients' health and quality of life. Health systems can utilize this data to analyze trends and recognize areas of opportunity so that measures can be taken to improve patient care.

Recommendations for optimizing the use of cytology in the diagnosis and management of patients with lung cancer.

Non-small cell lung cancer (NSCLC) is one of the oncological entities with the greatest evolution in molecular diagnosis due to the large number of diagnostic biomarkers and new treatments approved by international regulatory agencies. An accurate, early diagnosis using the least amount of tissue is the goal for the establishing and developing precision medicine for these patients. Rapid on-site evaluation (ROSE) provides cytological samples of optimal quantity and quality for a complete diagnosis of NSCLC. The usefulness of cytological samples has been demonstrated, not only for massive parallel sequencing but also for the quantification of the expression of programmed death-ligand 1 (PD-L1) and tumour mutational burden (TMB). Pre-analytical, analytical, and post-analytical recommendations are made for the management and appropriate use of cytological samples in order to obtain all the information necessary for the diagnosis and treatment of patients with NSCLC according to current quality parameters.

Percutaneous osteosynthesis of acetabular fractures with quadrilateral plate involvement using an infra-pectineal plate through a new paramedial approach: Description of the technique using cadaveric specimens.

Percutaneous osteosynthesis of acetabular fractures with quadrilateral plate involvement using an infra-pectineal plate through a new paramedial approach using cadaveric specimens. BACKGROUND: Intrapelvic approaches and infrapectineal plates have been used since the mid-nineties to solve Quadrilateral Plate osteosynthesis, with some problems in applying screws in the correct direction and difficulty in fracture reduction. We describe a minimally invasive paramedial approach and new ways to fix infrapectineal plates using one-step osteosynthesis (reduction and fixation). METHODS: Four transverse and four posterior hemitransverse acetabular fractures were reproduced using four fresh frozen cadavers. Acetabular osteosynthesis was performed using the paramedial approach. Sequential lasting time and reduction/stability quality were measured using analysis of variance (ANOVA) with Bonferroni Correction as the statistical method, registering iatrogenic injuries. RESULTS: Osteosynthesis was performed on seven acetabulae using infrapectineal horizontal plates for transverse fractures and vertical plates for posterior hemitransverse fractures. The duration of incision was 3:08 min and osteosynthesis was 55:12 min, with a total of 58:29 min. Median fracture displacement of 13.25 mm turned to a median of 0.01 mm once fracture osteosynthesis was performed with a p = 0.017. The peritoneum was injured twice and good osteosynthesis stability was observed. CONCLUSION: The paramedial approach is safe with direct access to key anatomical structures for acetabular osteosynthesis. Infrapectineal with reverse fixation plate osteosynthesis provides an excellent reduction rate and good stability once the implants act against displacement forces, making it possible to direct them freely. Further clinical and biomechanical trials are required to confirm our findings. We believe that there was an improvement of up to 60% in the result quality for some cases; however, this technique must be compared with other techniques. Evidence Level IV (Experimental Trial).

Mi PROTECT: A personalized smartphone platform to report back results to participants of a maternal-child and environmental health research cohort program in Puerto Rico.

BACKGROUND: The PROTECT Center is a multi-project initiative that studies the relationship between exposure to environmental contaminants and preterm births during the prenatal and postnatal period among women living in Puerto Rico. PROTECT's Community Engagement Core and Research Translation Coordinator (CEC/RTC) play a key role in building trust and capacity by approaching the cohort as an engaged community that provides feedback about processes, including how personalized results of their exposure to chemicals should be reported back. The goal of the Mi PROTECT platform was to create a mobile-based application of DERBI (Digital Exposure Report-Back Interface) for our cohort that provides tailored, culturally appropriate information about individual contaminant exposures as well as education on chemical substances and approaches to exposure reduction. METHODS: Participants (N = 61) were presented with commonly used terms in environmental health research related to collected samples and biomarkers, followed by a guided training on accessing and exploring the Mi PROTECT platform. Participants evaluated the guided training and Mi PROTECT platform answering a Likert scale in separated surveys that included 13 and 8 questions, respectively. RESULTS: Participants provided overwhelmingly positive feedback on the clarity and fluency of presenters in the report-back training. Most participants reported that the mobile phone platform was both accessible and easy to navigate (83% and 80%, respectively) and that images included in the platform facilitated comprehension of the information. Overall, most participants (83%) reported that language, images, and examples in Mi PROTECT strongly represented them as Puerto Ricans. CONCLUSIONS: Findings from the Mi PROTECT pilot test informed investigators, community partners and stakeholders by demonstrating a new way to promote stakeholder participation and foster the "research right-to-know."