ALK Inhibition With Alectinib for Refractory Metastatic Renal Cell Carcinoma With ALK Rearrangement: A Rare Case Report and Literature Review.

ALK-rearranged RCC refractory to several lines of treatment has a durable response when treated with alectinib.

Cephalometric analysis performance discrepancy between orthodontists and an artificial intelligence model using lateral cephalometric radiographs.

PURPOSE: The purpose of the present clinical study was to compare the Ricketts and Steiner cephalometric analysis obtained by two experienced orthodontists and artificial intelligence (AI)-based software program and measure the orthodontist variability. MATERIALS AND METHODS: A total of 50 lateral cephalometric radiographs from 50 patients were obtained. Two groups were created depending on the operator performing the cephalometric analysis: orthodontists (Orthod group) and an AI software program (AI group). In the Orthod group, two independent experienced orthodontists performed the measurements by performing a manual identification of the cephalometric landmarks and a software program (NemoCeph; Nemotec) to calculate the measurements. In the AI group, an AI software program (CephX; ORCA Dental AI) was selected for both the automatic landmark identification and cephalometric measurements. The Ricketts and Steiner cephalometric analyses were assessed in both groups including a total of 24 measurements. The Shapiro-Wilk test showed that the data was normally distributed. The t-test was used to analyze the data (α = 0.05). RESULTS: The t-test analysis showed significant measurement discrepancies between the Orthod and AI group in seven of the 24 cephalometric parameters tested, namely the corpus length (p = 0.003), mandibular arc (p < 0.001), lower face height (p = 0.005), overjet (p = 0.019), and overbite (p = 0.022) in the Ricketts cephalometric analysis and occlusal to SN (p = 0.002) and GoGn-SN (p < 0.001) in the Steiner cephalometric analysis. The intraclass correlation coefficient (ICC) between both orthodontists of the Orthod group for each cephalometric measurement was calculated. CONCLUSIONS: Significant discrepancies were found in seven of the 24 cephalometric measurements tested between the orthodontists and the AI-based program assessed. The intra-operator reliability analysis showed reproducible measurements between both orthodontists, except for the corpus length measurement. CLINICAL SIGNIFICANCE: The artificial intelligence software program tested has the potential to automatically obtain cephalometric analysis using lateral cephalometric radiographs; however, additional studies are needed to further evaluate the accuracy of this AI-based system.

Micellar liquid chromatography as a sustainable tool to quantify three statins in oral solid dosage forms.

A method based on micellar liquid chromatography has been developed to determine rosuvastatin, lovastatin and simvastatin in oral solid dosage forms. Samples were solved in mobile phase up to the target concentration, filtered and directly injected. The three statins were resolved in 30 min, using an aqueous solution of 0.10 M sodium dodecyl sulfate - 7.0% 1-butanol, buffered at pH 3 with 0.01 M phosphate salt as mobile phase, running under isocratic mode at 1 mL/min through a C18 column. Detection was at 240 nm. The effect of sodium dodecyl sulfate on elution strength was more important than that of the organic solvent. The procedure was successfully validated by the guidelines of the International Council for Harmonization in terms of: specificity, linearity (r2 > 0.990), calibration range (1.5 - 15 mg/L for rosuvastatin, 0.5-10 mg/L for lovastatin and simvastatin), limit of detection (0.4, 0.2 and 0.15 mg/L for rosuvastatin, lovastatin and simvastatin, respectively), trueness (98.8-101.7%), precision (<2.7%), carry-over effect, robustness, and stability. Values were inside the acceptance criteria of the Methods, Method Verification and Validation, Food and Drug Administration-Office of Regulatory Affairs, thus ensuring the reliability of the results. The main feature was the low proportion of organic solvent used, thus making the procedure sustainable and green. Besides, it was easy-to-conduct and with high sample-throughput, and then useful for routine analysis in pharmaceutical quality control. Finally, it was applied to commercial pharmaceutical preparations.

The Potential Revolution of Cancer Treatment with CRISPR Technology.

Immuno-oncology (IO) and targeted therapies, such as small molecule inhibitors, have changed the landscape of cancer treatment and prognosis; however, durable responses have been difficult to achieve due to tumor heterogeneity, development of drug resistance, and adverse effects that limit dosing and prolonged drug use. To improve upon the current medicinal armamentarium, there is an urgent need for new ways to understand, reverse, and treat carcinogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 is a powerful and efficient tool for genome editing that has shown significant promise for developing new therapeutics. While CRISPR/Cas9 has been successfully used for pre-clinical cancer research, its use in the clinical setting is still in an early stage of development. The purpose of this review is to describe the CRISPR technology and to provide an overview of its current applications and future potential as cancer therapies.

Construction and Evaluation of a Realistic Low-Cost Model for Training in Chest-Tube Insertion.

INTRODUCTION: Emergency thoracostomy is applied in life-threatening situations. Simulation plays a pivotal role in training in invasive techniques used mainly in stressful situations. Currently available commercial simulation models for thoracostomy have various drawbacks. METHODS: We designed a thoracostomy phantom from discarded hospital materials and pigskin with underlying flesh. The phantom can be used alone for developing technical skills or mounted on an actor in simulation scenarios. Medical students, intensive care unit (ICU) and emergency department teams, and thoracostomy experts evaluated its technical fidelity and usefulness for achieving learning objectives in workshops. RESULTS: The materials used to construct the phantom cost €47. A total of 12 experts in chest-tube placement and 73 workshop participants (12 ICU physicians and nurses, 20 emergency physicians and nurses, and 41 fourth-year medical students) evaluated the model. All groups rated the model's usefulness and the sensation of perforating the pleura highly. Experts rated the air release after pleura perforation lower than other groups. Lung reexpansion was the lowest rated item in all groups. Ratings of the appearance and feel of the model correlated strongly among all groups and experts. The ICU professionals rated the resistance encountered in introducing the chest drain lower than the other groups. CONCLUSIONS: This low-cost, reusable, transportable, and highly realistic model is an attractive alternative to commercial models for training in chest-tube insertion skills.

Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder.

Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations.

MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.

Methylthioadenosine phosphorylase, an essential enzyme for the adenine salvage pathway, is often deficient (MTAPdef) in tumors with 9p21 loss and hypothetically renders tumors susceptible to synthetic lethality by antifolates targeting de novo purine synthesis. Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAPdef urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAPdef patients show response to pemetrexed (ORR 43%). Furthermore, a historic cohort shows 4 of 4 MTAPdef patients respond to pemetrexed as compared to 1 of 10 MTAP-proficient patients. In vitro and in vivo preclinical data using UC cell lines demonstrate increased sensitivity to pemetrexed by inducing DNA damage, and distorting nucleotide pools. In addition, MTAP-knockdown increases sensitivity to pemetrexed. Furthermore, in a lung adenocarcinoma retrospective cohort (N = 72) from the published BATTLE2 clinical trial (NCT01248247), MTAPdef associates with an improved response rate to pemetrexed. Our data demonstrate a synthetic lethal interaction between MTAPdef and de novo purine inhibition, which represents a promising therapeutic strategy for larger prospective trials.

SOX9 Triggers Different Epithelial to Mesenchymal Transition States to Promote Pancreatic Cancer Progression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers mainly due to spatial obstacles to complete resection, early metastasis and therapy resistance. The molecular events accompanying PDAC progression remain poorly understood. SOX9 is required for maintaining the pancreatic ductal identity and it is involved in the initiation of pancreatic cancer. In addition, SOX9 is a transcription factor linked to stem cell activity and is commonly overexpressed in solid cancers. It cooperates with Snail/Slug to induce epithelial-mesenchymal transition (EMT) during neural development and in diseases such as organ fibrosis or different types of cancer. METHODS: We investigated the roles of SOX9 in pancreatic tumor cell plasticity, metastatic dissemination and chemoresistance using pancreatic cancer cell lines as well as mouse embryo fibroblasts. In addition, we characterized the clinical relevance of SOX9 in pancreatic cancer using human biopsies. RESULTS: Gain- and loss-of-function of SOX9 in PDAC cells revealed that high levels of SOX9 increased migration and invasion, and promoted EMT and metastatic dissemination, whilst SOX9 silencing resulted in metastasis inhibition, along with a phenotypic reversion to epithelial features and loss of stemness potential. In both contexts, EMT factors were not altered. Moreover, high levels of SOX9 promoted resistance to gemcitabine. In contrast, overexpression of SOX9 was sufficient to promote metastatic potential in K-Ras transformed MEFs, triggering EMT associated with Snail/Slug activity. In clinical samples, SOX9 expression was analyzed in 198 PDAC cases by immunohistochemistry and in 53 patient derived xenografts (PDXs). SOX9 was overexpressed in primary adenocarcinomas and particularly in metastases. Notably, SOX9 expression correlated with high vimentin and low E-cadherin expression. CONCLUSIONS: Our results indicate that SOX9 facilitates PDAC progression and metastasis by triggering stemness and EMT.

Frecuencia de depresión y calidad de vida en pacientes con diabetes mellitus en establecimientos de salud pública de Lima Metropolitana / Frequency of depression and quality of life in patients with diabetes mellitus in public health facilities in metropolitan Lima

RESUMEN Introducción: La diabetes es una de las principales pandemias en los últimos anos. Su asociación con depresión incrementa el riesgo de mortalidad y morbilidad. La coexistencia de ambas patologías produce un mal manejo de la diabetes, lo que conlleva a una peor calidad de vida. Objetivo: Determinar la frecuencia de depresión en pacientes con diabetes mellitus y el efecto que tienen ambas patologías sobre la calidad de vida en pacientes que acuden de forma ambulatoria a establecimientos de salud públicos de Lima y Callao. Métodos: Análisis secundario de la base de datos del Estudio Epidemiológico de Salud Mental de depresión en adultos diabéticos. El instrumento empleado para determinar el episodio depresivo fue el MINI (Entrevista Neuropsiquiátrica Internacional) mientras que la calidad de vida fue medida empleando el Índice de Calidad de Vida de Mezzich. Se obtuvo información de diagnóstico de diabetes tipo1ó2del registro médico diario (HIS) de atención. Resultados: La frecuencia de depresión en los 471 pacientes con diabetes fue 5,8% en las últimas dos semanas. Mientras que la frecuencia anual fue 8,6% y en algún momento de la vida 31,8%. Ser mujer se asoció con mayor frecuencia de depresión. La calidad de vida fue menor en los pacientes con diabetes y depresión (p<0,005). Conclusiones: La frecuencia de depresión en pacientes con diabetes que son atendidos en forma ambulatoria en centros de salud públicos es mayor a la población general y su calidad de vida se ve reducida significativamente, lo que plantea la necesidad de considerar la depresión como un factor aditivo a la carga de morbilidad de esta condición.

ABSTRACT Introduction: Diabetes is one of the main pandemics in recent years. Its association with depression increases the risk of mortality and morbidity. The coexistence of both diseases leads to poor management of diabetes, which leads to a worse quality of life. Objective: To determine the frequency of depression in patients with diabetes mellitus and the effect of both pathologies on the quality of life in patients who attend outpatient appointments at public health facilities in Lima and Callao. Methodology: Secondary analysis of the Epidemiological Study of Mental Health of depression in diabetic adults. The instrument used to determine the depressive episode was the MINI (Mini-International Neuropsychiatric Interview) while quality of life was measured using the Mezzich Quality of Life Index. Diagnosis information of type 1 or 2 diabetes was obtained from the daily medical record (HIS) of care. Results: The frequency of depression in the 471 patients with diabetes was 5.8% in the last two weeks. While the annual frequency was 8.6% and 31.8% at some point in life. Being a woman was associated with a greater frequency of depression. Quality of life was lower in patients with diabetes and depression (p < 0.005). Conclusions: The frequency of depression in patients with diabetes who are treated on an outpatient basis in public health centres is higher than the general population and their quality of life is significantly reduced, which raises the need for considering depression as an additional factor to the burden of morbidity of this condition.

Frequency of depression and quality of life in patients with diabetes mellitus in public health facilities in Metropolitan Lima.

INTRODUCTION: Diabetes is one of the main pandemics in recent years. Its association with depression increases the risk of mortality and morbidity. The coexistence of both diseases leads to poor management of diabetes, which leads to a worse quality of life. OBJECTIVE: To determine the frequency of depression in patients with diabetes mellitus and the effect of both pathologies on the quality of life in patients who attend outpatient appointments at public health facilities in Lima and Callao. METHODOLOGY: Secondary analysis of the Epidemiological Study of Mental Health of depression in diabetic adults. The instrument used to determine the depressive episode was the MINI (Mini-International Neuropsychiatric Interview) while quality of life was measured using the Mezzich Quality of Life Index. Diagnosis information of type 1 or 2 diabetes was obtained from the daily medical record (HIS) of care. RESULTS: The frequency of depression in the 471 patients with diabetes was 5.8% in the last two weeks. While the annual frequency was 8.6% and 31.8% at some point in life. Being a woman was associated with a greater frequency of depression. Quality of life was lower in patients with diabetes and depression (p < 0.005). CONCLUSIONS: The frequency of depression in patients with diabetes who are treated on an outpatient basis in public health centres is higher than the general population and their quality of life is significantly reduced, which raises the need for considering depression as an additional factor to the burden of morbidity of this condition.

Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate.

BACKGROUND: Currently, there is no formally accepted pharmacological treatment for COVID-19. MATERIALS AND METHODS: We included COVID-19 outpatients of a Peruvian primary care center from Lima, Peru, who were treated between April 30 - September 30, 2020, with hydroxychloroquine and azithromycin. Logistic regression was applied to determine factors associated with case-fatality rate. RESULTS: A total of 1265 COVID-19 patients with an average age of 44.5 years were studied. Women represented 50.1% of patients, with an overall 5.9 symptom days, SpO2 97%, temperature of 37.3 °C, 41% with at least one comorbidity and 96.1% one symptom or sign. No patient treated within the first 72 h of illness died. The factors associated with higher case fatality rate were age (OR = 1.06; 95% CI 1.01-1.11, p = 0.021), SpO2 (OR = 0.87; 95% CI 0.79-0.96, p = 0.005) and treatment onset (OR = 1.16; 95% CI 1.06-1.27, p = 0.002), being the latter the only associated in the multivariate analysis (OR = 1.18; 95% CI 1.05-1.32, p = 0.005). 0.6% of our patients died. CONCLUSIONS: The case fatality rate in COVID-19 outpatients treated with hydroxychloroquine/azithromycin was associated with the number of days of illness on which treatment was started.

Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors.

Importance: Immune checkpoint inhibitors can produce distinct toxic effects that require prompt recognition and timely management. Objective: To develop a technology-enabled, dynamically adaptive protocol that can provide the accurate information needed to inform specific remedies for immune toxic effects in patients treated with immune checkpoint inhibitors. Design, Setting, and Participants: An open-label cohort study was conducted at a single tertiary referral center from September 6, 2019, to September 3, 2020. The median follow-up duration was 63 (interquartile range, 35.5-122) days. Fifty patients with genitourinary cancers treated with immune checkpoint inhibitors were enrolled. Interventions: A fit-for-purpose electronic platform was developed to enable active patient and care team participation. A smartphone application downloaded onto patients' personal mobile devices prompted them to report their symptoms at least 3 times per week. The set of symptoms and associated queries were paired with alert thresholds for symptoms requiring clinical action. Main Outcomes and Measures: The primary end point of this interim analysis was feasibility, as measured by patient and care team adherence, and lack of increase in care team staffing. Operating characteristics were estimated for each symptom alert and used to dynamically adapt the alert thresholds to ensure sensitivity while reducing unnecessary alerts. Results: Of the 50 patients enrolled, 47 had at least 1 follow-up visit and were included in the analysis. Median age was 65 years (range, 37-86), 39 patients (83%) were men, and 39 patients (83%) had metastatic cancer, with the most common being urothelial cell carcinoma and renal cell carcinoma (22 [47%] patients each). After initial onboarding, no further care team training or additional care team staffing was required. Patients had a median study adherence rate of 74% (interquartile range, 60%-86%) and 73% of automated alerts were reviewed within 3 days by the clinic team. Symptoms with the highest positive predictive value for adverse events requiring acute intervention included dizziness (21%), nausea/vomiting (26%), and shortness of breath (14%). The symptoms most likely to result in unnecessary alerts were arthralgia and myalgia, fatigue, and cough. Conclusions and Relevance: The findings of this cohort study suggest an acceptable and fiscally sound method can be developed to create a dynamic learning system to detect and manage immune-related toxic effects.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of urothelial cancer.

A number of immunotherapies have been developed and adopted for the treatment of urothelial cancer (encompassing cancers arising from the bladder, urethra, or renal pelvis). For these immunotherapies to positively impact patient outcomes, optimal selection of agents and treatment scheduling, especially in conjunction with existing treatment paradigms, is paramount. Immunotherapies also warrant specific and unique considerations regarding patient management, emphasizing both the prompt identification and treatment of potential toxicities. In order to address these issues, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts in the field of immunotherapy for urothelial cancer. The expert panel developed this clinical practice guideline (CPG) to inform healthcare professionals on important aspects of immunotherapeutic treatment for urothelial cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with urothelial cancer.

Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease.

INTRODUCTION: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). METHOD: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. RESULTS: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86-1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60-0.97). CONCLUSION: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.

Percepción estudiantil sobre la guardia médica como forma de educación en el trabajo / Student perception on the doctor on duty system as a form of in- service training

RESUMEN Fundamento: la guardia médica en pregrado constituye un escenario formativo para la adquisición de habilidades y valores propios de la carrera de Medicina. Objetivo: valorar la guardia médica como forma de educación en el trabajo según la percepción de estudiantes de quinto año de Medicina. Método: se realizó una investigación descriptiva y transversal en la Universidad de Ciencias Médicas de Pinar del Río durante 2019-2020. Se aplicaron métodos teóricos: análisis-síntesis, inducción-deducción e histórico-lógico; empíricos: cuestionario a estudiantes mediante el cual se exploraron sus opiniones sobre la guardia médica. Los resultados obtenidos se llevaron a tablas para sus análisis, a los que se les aplicó el método porcentual. Resultados: los estudiantes consideraron la guardia médica como una forma de vincular la adquisición de conocimientos, habilidades y hábitos para la solución de los problemas de salud en la comunidad; las especialidades Cirugía, Ginecología y Otorrinolaringología fueron las más reconocidas por sus aportes a la profesión; señalaron como mayores habilidades obtenidas: interrogar al paciente, confeccionar historias clínicas y buscar factores de riesgo; la mayoría coincidieron en opinar sobre la efectividad del control y evaluación docentes, aunque persistieron algunas deficiencias metodológicas para lograr una mayor motivación en ellos. Conclusiones: los estudiantes percibieron la efectividad de la guardia médica como forma de educación en el trabajo en la carrera de Medicina, pues opinaron favorablemente sobre ella a partir de los aportes ofrecidos en cuanto a solidez del aprendizaje, y en la concepción y desarrollo de habilidades y valores profesionales.

ABSTRACT Background: the undergraduate medical student on duty system constitutes a formative scene for the acquisition of skills and values ​​of the Medicine degree. Objective: to assess the medical student on duty system as a form of in-service training according to the perception of fifth-year medical students. Method: a descriptive and cross-sectional research was carried out at Pinar del Río University of Medical Sciences from 2019 to 2020. Theoretical methods were applied: analysis-synthesis, induction-deduction and historical-logical; empirical ones: questionnaire to students through which their opinions about the medical student on duty system were explored. The results were illustrated through tables where the percentage method was applied for analysis. Results: the students considered the medical on call system as a way to link the acquisition of knowledge, skills and habits for the solution of health problems in the community; Surgery, Gynecology and Otorhinolaryngology specialties were the most recognized for their contributions to the profession; They pointed out as greater skills obtained: questioning the patient, making medical records and looking for risk factors; The majority agreed in their opinion on the effectiveness of teacher control and evaluation, although some methodological deficiencies persisted in order to achieve greater motivation in them. Conclusions: the students perceived the effectiveness of the medical on call system as a form of in-service training in the Medicine degree, since they gave a favorable opinion about it based on the contributions offered in terms of solidity of learning and in the conception and development of skills and professional values.

Acute Altitude Acclimatization in Young Healthy Volunteers: Nocturnal Oxygenation Increases Over Time, Whereas Periodic Breathing Persists.

Ju, Jia-Der, Cristian Zhang, Francis P. Sgambati, Lidia M. Lopez, Luu V. Pham, Alan R. Schwartz, and Roberto A. Accinelli. Acute altitude acclimatization in young healthy volunteers: nocturnal oxygenation increases over time whereas periodic breathing persists. High Alt Med Biol. 22:14-23, 2021. Study Objectives: This study aimed to examine the acute effects of high altitude (HA) on sleep disordered breathing (sleep apnea and nocturnal hypoxemia) and acute mountain sickness and to characterize acclimatization over time. Methods: Ten native lowlanders residing at sea level (SL) completed the Lake Louise Score (LLS) and underwent nocturnal polygraphy (ApneaLink Plus) for nine consecutive nights (N1-N9) at HA (2,761 m) and two nights before and after HA. Nocturnal oxygen profiles were assessed by measuring the mean nocturnal oxyhemoglobin saturation (SpO2) during sleep, and sleep apnea severity as assessed by measuring the Apnea-Hypopnea Index (AHI). Mixed-effects linear regression was used to model responses in outcomes (mean nocturnal SpO2, logAHI, and LLS) between HA and SL. Changes in SpO2 and AHI were examined in subgroups with mild versus marked nocturnal SpO2 and low versus high AHI during exposure to HA and compared between subgroups. Results: Compared with SL, the mean nocturnal SpO2 was lower (p < 0.0001) and AHI was higher (p < 0.0001) at HA. The mean nocturnal SpO2 increased progressively (p < 0.001), whereas AHI remained high (p < 0.978) and relatively unchanged over nine successive nights at HA. Those with markedly reduced SpO2 upon arrival at HA exhibited progressive increases in the mean nocturnal SpO2 over time at HA compared with those with mild nocturnal desaturation. LLS rose at HA, but no differences were observed between subgroups. Conclusions: In healthy HA sojourners, the mean nocturnal SpO2 increased progressively over time, whereas AHI remained elevated, suggesting distinctive phenotypes and acclimatization responses to HA.

Frequency of Depression and Quality of Life in Patients with Diabetes Mellitus in Public Health Facilities in Metropolitan Lima. / Frecuencia de depresión y calidad de vida en pacientes con diabetes mellitus en establecimientos de salud pública de Lima Metropolitana.

INTRODUCTION: Diabetes is one of the main pandemics in recent years. Its association with depression increases the risk of mortality and morbidity. The coexistence of both diseases leads to poor management of diabetes, which leads to a worse quality of life. OBJECTIVE: To determine the frequency of depression in patients with diabetes mellitus and the effect of both pathologies on the quality of life in patients who attend outpatient appointments at public health facilities in Lima and Callao. METHODOLOGY: Secondary analysis of the Epidemiological Study of Mental Health of depression in diabetic adults. The instrument used to determine the depressive episode was the MINI (Mini-International Neuropsychiatric Interview) while quality of life was measured using the Mezzich Quality of Life Index. Diagnosis information of type 1 or 2 diabetes was obtained from the daily medical record (HIS) of care. RESULTS: The frequency of depression in the 471 patients with diabetes was 5.8% in the last two weeks. While the annual frequency was 8.6% and 31.8% at some point in life. Being a woman was associated with a greater frequency of depression. Quality of life was lower in patients with diabetes and depression (p <0.005). CONCLUSIONS: The frequency of depression in patients with diabetes who are treated on an outpatient basis in public health centres is higher than the general population and their quality of life is significantly reduced, which raises the need for considering depression as an additional factor to the burden of morbidity of this condition.

A systematic review of the accuracy and efficiency of dental movements with Invisalign®.

We are currently living in an era where the use of computer-aided design/computer-aided manufacturing has allowed individualized orthodontic treatments, but has also incorporated enhanced digitalized technology that does not permit improvisation. The purpose of this systematic review was to analyze publications that assessed the accuracy and efficiency of the Invisalign® system. A systematic review was performed using a search strategy to identify articles that referenced Invisalign®, which were published between August 2007 and August 2017, and listed in the following databases: MEDLINE, Embase, Cochrane Library, Web of Knowledge, Google Scholar, and LILACS. Additionally, a manual search of clinical trials was performed in scientific journals and other databases. To rate the methodological quality of the articles, a grading system described by the Swedish Council on Technology Assessment in Health Care was used, in combination with the Cochrane tool for risk of bias assessment. We selected 20 articles that met the inclusion criteria and excluded 5 due to excess biases. The level of evidence was high. Although it is possible to treat malocclusions with plastic systems, the results are not as accurate as those achieved by treatment with fixed appliances.

Effectiveness and safety of moderate-intensity aerobic water exercise during pregnancy for reducing use of epidural analgesia during labor: protocol for a randomized clinical trial.

BACKGROUND: Epidural analgesia during labor can provide effective pain relief, but can also lead to adverse effects. The practice of moderate exercise during pregnancy is associated with an increased level of endorphins in the blood, and this could also provide pain relief during labor. Aerobic water exercises, rather than other forms of exercise, do not negatively impact articulations, reduce edema, blood pressure, and back pain, and increase diuresis. We propose a randomized controlled trial (RCT) to evaluate the effectiveness and safety of a moderate water exercise program during pregnancy on the need for epidural analgesia during labor. METHODS: A multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. We will randomised 320 pregnant women (14 to 20 weeks gestation) who have low risk of complications to a moderate water exercise program or usual care. DISCUSSION: The findings of this research will contribute toward understanding of the effects of a physical exercise program on pain and the need for analgesia during labor. TRIAL REGISTRATION: ISRCTN Registry identifier: 14097513 register on 04 September 2017. Retrospectively registered.