GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis.

Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson's disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Normative values of motor performance and their relationship with BMI status in Hong Kong preschoolers.

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3-5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Improved Clinical Outcomes With Dynamic, Force-Controlled, Gap-Balancing in Posterior-Stabilized Total Knee Arthroplasty.

BACKGROUND: Optimal soft-tissue management in total knee arthroplasty (TKA) may reduce symptomatic instability. We hypothesized that TKA outcomes using a computer-assisted dynamic ligament balancer that acquires medial and lateral gap sizes throughout the motion arc would show improved Knee Society Scores (KSS) compared to TKAs done with a traditional tensioner at 0 and 90°. We also sought to quantify the degree to which the planned femoral rotation chosen to optimize medio-lateral balance throughout the arc of motion deviated from the femoral rotation needed to achieve a rectangular flexion gap at 90° alone. METHODS: Baseline demographics, clinical outcomes, KSSs, and femoral rotations were compared in 100 consecutive, computer-assisted TKAs done with the balancer (balancer group) to the immediately prior 100 consecutive computer-assisted TKAs done without the balancer (control group). Minimum follow-up was 13 months and all patients had osteoarthritis. Mean knee motion did not differ preoperatively (110.1 ± 13.6° balancer, 110.4 ± 12.5° control, P = .44) or postoperatively (119.1 ± 10.3° balancer, 118.8 ± 10.9° control, P = .42). Tourniquet times did not differ (93.1 ± 13.0 minutes balancer, 90.7 ± 13.0 minutes control, P = .13). Postoperative length of stay differed (40.2 ± 20.9 hours balancer, 49.0 ± 18.3 hours control, P = .0009). There were 14 readmissions (7 balancer, 7 control), 11 adverse events (4 balancer, 7 control), and 3 manipulations (1 balancer, 2 control). The cohorts were compared using Student's t-tests, Shapiro-Wilk normalities, Wilcoxon rank-sums, and multivariable logistic regression analyses. RESULTS: Postoperative KSS improvements were higher in the balancer group (P < .0001). In multivariable regression analyses, the balancer group experienced 7 ± 2 point improvement in KSS Knee scores (P < .0001) and 4 ± 2 point improvement in KSS Function scores (P = .040) compared to the control group. CONCLUSIONS: The statistically and clinically significant improvements in postoperative KSS demonstrated in the balancer cohort are likely driven by improved stability throughout the motion arc. Further study is warranted to evaluate replicability by non-design surgeons.

Effect of a Mobile Game-Based Intervention to Enhance Child Safety: Randomized Controlled Trial.

BACKGROUND: Evidence supports the effectiveness of serious games in health education, but little is known about their effects on the psychosocial well-being of children in the general population. OBJECTIVE: This study aimed to investigate the potential of a mobile game-based safety education program in improving children's safety and psychosocial outcomes. METHODS: Safe City is a mobile roleplaying game specifically designed to educate children in Hong Kong about safety. This randomized controlled trial included 340 children in grades 4 through 6. Intervention arm participants (n=170) were instructed to play the Safe City mobile game for 4 weeks, whereas control arm participants (n=170) received a safety booklet. All participants completed a survey on safety knowledge and behaviors and psychosocial problems at baseline (T1), 1 month postintervention (T2), and 3 months postintervention (T3). Cumulative game scores and mini-game performance were analyzed as a proxy for the extent of exposure to the game. Outcome data were analyzed using 2-sample 2-tailed t tests to compare mean change from T1 to T2 and to T3 for intervention versus control arm participants. The association of game use with outcome changes postintervention was analyzed using generalized additive models. RESULTS: No significant differences were found in mean changes between the intervention and control arms. However, use analyses showed that higher game scores were associated with improvements in safe behavior (P=.03) and internalizing problems (P=.01) at T3. Matching and Spot the Danger mini-game performance significantly predicted improvements in safety knowledge at T2 and T3. CONCLUSIONS: Analysis of use has shown that playing the Safe City mobile game can result in significant improvements in safety knowledge and reductions in unsafe behavior and internalizing problems. These findings provide evidence for the positive impact of serious games on psychological and social well-being, highlighting the potential of technology-driven interventions to assist children in learning about safety and preventing injuries. TRIAL REGISTRATION: ClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/17756.

Longitudinal associations between child discipline methods and physical growth patterns across preschool years.

OBJECTIVE: Research has documented the associations of child maltreatment with a range of physical health problems, but little is known about the physical growth patterns of children who experience maltreatment in early childhood. This study aimed to examine the association between various discipline approaches and physical growth in preschool-aged children. METHODS: In the first year of preschool, parents of 661 Chinese preschool-aged children completed a questionnaire with items pertaining to the frequency of using physical maltreatment, psychological aggression, neglect, and nonviolent discipline toward the child. Children's weight and height were assessed annually using direct assessment in the first and two subsequent years. Longitudinal analyses were performed using multiple regression models. RESULTS: More frequent neglect and psychological aggression during the first year of preschool were associated with a higher likelihood of a decreased BMI z score in subsequent years. Conversely, increased experience of physical maltreatment in the first year was associated with an increased likelihood of having overweight or obesity in the third year. CONCLUSIONS: Results indicate that early maltreatment experience can impact physical growth. This highlights the importance of preventing abusive parenting and encouraging healthy habits in young children who have experienced maltreatment to decrease their future risk for weight problems.

Pain Scales: What Are They and What Do They Mean.

PURPOSE OF REVIEW: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages. RECENT FINDINGS: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings. CONCLUSION: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population.

Association of vitamin D-binding protein polymorphisms and serum 25(OH)D concentration varies among Chinese healthy infants of different VDR-FokI genotypes: A multi-centre cross-sectional study.

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants.

Identification of an Unmet Medical Need: Height of Depression, Hypersomnia, and Sleep Apnea Positively Correlate With the Level of Fatigue in Patients With Immune Thrombocytopenia.

INTRODUCTION: Immune thrombocytopenia (ITP) is a rare chronic disease, frequently accompanied by fatigue, which is an important comorbidity associated with this disease. Patients experience difficulties in managing their daily activities and a reduction in their overall quality of life (QoL). The causes of fatigue in ITP are not clarified yet, and underlying causes seem to be multifactorial. The development of fatigue may not solely be influenced by a decrease in platelet count but also by unknown factors as well as psychological reasons. METHODS: This prospective, multicenter, exploratory, pilot study aimed to investigate which parameters contribute to the occurrence of fatigue in patients with ITP. Adult patients with ITP and with or without fatigue who visited the study center for their regular appointments were asked to complete questionnaires pertaining to patient-reported outcome measures regarding bleeding symptoms, depression, sleep apnea, and hypersomnia. Blood tests included platelet count as well as different parameters like vitamin D. RESULTS: A total of 36 patients (100%; 27 females (75%) and nine males (25%)) with primary ITP, with a median age of 46.5 years (range 19­83 years) were analyzed. The median duration of ITP was 4.5 years (min­max 0-21). Approximately one-third of patients (29.4%; 10/34 patients) had no comorbidities. The two most frequently used current treatment options were "watch-and-wait" (38.9%; 14/36 patients) and "avatrombopag" (30.6%; 11/36 patients); eight patients (22.2%; 8/36 patients) needed rescue therapy with corticosteroids. There was a statistically negative correlation between fatigue and year of diagnosis (r=-0.41, p=0.014). Results indicated no statistically significant relationship between fatigue and age or differences in fatigue between the genders. Ferritin predicted fatigue with statistical significance. Platelet count was not correlated with the level of fatigue. A significant correlation was obvious between fatigue, depression, and obstructive sleep apnea syndrome (OSAS) as well as sleep-related problems (p<0.01). DISCUSSION: Patient characteristics were comparable to that of other studies. The level of fatigue negatively impacts the lives of patients with ITP. Age and gender were not correlated with fatigue in ITP, which is in line with other reports. Interestingly, the fatigue level was higher in patients presenting with additional depression and poor sleeping quality due to, e.g., hypersomnia, which seems common. Fatigue levels seem independent from thrombocyte levels, which were reported elsewhere. CONCLUSION: Patients diagnosed with ITP several years ago cope with their condition better than patients with a more recent diagnosis, who have higher levels of fatigue. Concurrent depression, hypersomnia, and sleep apnea are important underestimated factors, which do have a negative effect on the QoL of patients with ITP. We were able to show that patients with ITP might face an unmet medical need in terms of delayed diagnosis and supportive therapy. To our knowledge, this is the first report on combined findings of depression, hypersomnia, and sleep apnea in patients with ITP.

Hepatitis C virus prevalence among men who have sex with men: a cross-sectional study in 12 Brazilian cities.

BACKGROUND: Despite the preventive policies adopted, reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) has been limited. The risk of hepatitis C virus (HCV) infection has increased among the most vulnerable population groups, including MSM. The aim of this study was to estimate the prevalence of HCV infection and to assess risky practices among MSM from 12 Brazilian cities. METHODS: This study was carried out from June to December 2016 using respondent driven sampling (RDS). Participants completed a self-administered questionnaire to collect behavioral, socioeconomic, and demographic variables. In addition, the rapid diagnostic test (RDT) for HCV was offered. Positive results were sent to Instituto Adolfo Lutz for confirmation. RESULTS: A total of 4,176 participants were recruited and 23 samples were sent for confirmation. Of these, 16 were confirmed, resulting in a prevalence of 0.7% (95% CI: 0.3%-1.7%). The Southeast region showed a prevalence of 0.9% (95% CI: 0.3-2.6), followed by the South region, with 0.6% (95% CI: 0.2-2.1). The Northeast region had a prevalence of 0.3% (95% CI: 0.1-1.0) and the Midwest 0.1% (95% CI: 0.0-0.7). No positive cases were found in the North. Single men aged 40 years or older were the majority of participants exposed to HCV. High levels of alcohol consumption, illicit drug use, irregular condom use, in addition to infection with other STIs, were associated with exposure to HCV. CONCLUSIONS: STIs continue to be important health problems in Brazil and globally. Many STIs are inapparent for many years until they bring more serious consequences. Extra investment in HCV is also warranted, given that it can be eliminated. Relying solely on clinical data to provide information about inapparent infection, especially in stigmatized populations, will make that goal more difficult to achieve. Surveillance studies, such as the one reported here need to be repeated over time to demonstrate trends and to provide information for evaluation, program and policies. Investments in the most vulnerable populations are critical to achieve the World Health Organization global health goals including the elimination of viral hepatitis by 2030.

Psychometric properties of the Brazilian-Portuguese version of the Falls Behavioral Scale in people with Parkinson's disease.

PURPOSE: To verify the psychometric properties of the Brazilian-Portuguese version of the Falls Behavioral (FaB-Brazil) Scale in Parkinson's disease (PD). MATERIAL AND METHODS: Participants (n = 96) were assessed by disease-specific, self-report and functional mobility measures. Internal consistency of the FaB-Brazil scale was evaluated using Cronbach's alpha and inter-rater and test-retest reliability using intraclass correlation coefficients (ICC). The standard error of measurement (SEM), minimal detectable change (MDC), ceiling and floor effects, and convergent and discriminative validity were evaluated. RESULTS: Internal consistency was moderate (α = 0.77). Excellent inter-rater (ICC = 0.90; p < 0.001) and test-retest (ICC = 0.91; p < 0.001) reliability were found. The SEM was 0.20 and MDC was 0.38. Ceiling and floor effects were not found. Convergent validity was established by the positive correlations between the FaB-Brazil scale and age, modified Hoehn and Yahr, PD duration, Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Motor Aspects of Experiences of Daily Living, Timed Up & Go and 8-item Parkinson's Disease Questionnaire, and negative correlations between the FaB-Brazil scale and community mobility, Schwab & England, and Activities-specific Balance Confidence scale. Females showed greater protective behaviors than males; recurrent fallers showed greater protective behaviors than non-recurrent fallers (p < 0.05). CONCLUSIONS: The FaB-Brazil scale is reliable and valid for assessing people with PD.

Fall-related behaviors should be part of the fall risk assessment of community-dwelling people with Parkinson's disease.The Brazilian-Portuguese version of the Fall Behavioral (FaB-Brazil) Scale is reliable and valid for assessing everyday behaviors and actions related to falling in community-dwelling people with Parkinson's disease.The FaB-Brazil scale may be used to tailor individualized fall prevention programs.

Children and adolescents with non-Hodgkin lymphoma in Brazil: A national survey identifies the challenges encountered and documents the diversity of care

ABSTRACT Introduction: Brazil has many inequities in the healthcare provided nationwide. Therefore, in order to access challenges in treatment, available resources and current practices, to identify barriers in delivering a good quality of care among Brazilian centers treating children and adolescents with Non-Hodgkin Lymphoma (NHL) and to generate a future prospective guideline, a customized online survey was distributed to pediatric hematologists and oncologists across the country. Results: A total of 97 surveys were completed (35% response rate), from 47 cities in all Brazilian regions and 79 units of care, with a median of 1 answer by the center (range 1 - 5). Most respondents work at an institution supported exclusively by public/philanthropic resources (58%), with an average of 5 to 9 new cases/year (49%), and 41% have 4 to 6 oncologists/centers. Additionally, 22% have no easy access to the intensive care unit, 26% have no access to Rasburicase, 28% have no access to Rituximabe as front-line therapy and 41% have unreliable methotrexate monitoring levels. Those differences cannot be explained thoroughly by regional wealth variances, nor by the financing model. Regarding the pathology service, 70% consider having reasonable quality assistance, but the timeframe to deliver diagnosis is satisfactory to 46%. There is no uniform management of care, with the current guideline from the Sociedade Brasileira de Oncologia Pediátrica being adopted by 54 to 59%, depending on the NHL subtype. Conclusion: This study provides insights into the heterogeneity of care among Brazilian centers. Recognizing those diversities will support the design of effective strategies and collaboration nationwide.

Sequence variants affecting voice pitch in humans.

The genetic basis of the human vocal system is largely unknown, as are the sequence variants that give rise to individual differences in voice and speech. Here, we couple data on diversity in the sequence of the genome with voice and vowel acoustics in speech recordings from 12,901 Icelanders. We show how voice pitch and vowel acoustics vary across the life span and correlate with anthropometric, physiological, and cognitive traits. We found that voice pitch and vowel acoustics have a heritable component and discovered correlated common variants in ABCC9 that associate with voice pitch. The ABCC9 variants also associate with adrenal gene expression and cardiovascular traits. By showing that voice and vowel acoustics are influenced by genetics, we have taken important steps toward understanding the genetics and evolution of the human vocal system.

Maternal n-3 PUFA Intake During Pregnancy and Perinatal Mental Health Problems: A Systematic Review of Recent Evidence.

PURPOSE OF REVIEW: Pregnant women are vulnerable to mental health problems. Increasing evidence shows that omega-3 polyunsaturated fatty acid (n-3 PUFA) intake during pregnancy is beneficial to maternal perinatal mental health. A systematic review is needed to examine the associations reported in recent studies. The objective of this review was to provide an updated review on the association of antenatal n-3 PUFA intake via different sources (seafood, fish, overall diet, and supplementation) with perinatal mental health problems including depression, anxiety, and psychological distress. RECENT FINDINGS: Searches were performed in Web of Science, Embase, PubMed, and APA PsycInfo databases on 21 June 2021. A total of 2133 records were screened. Data including the name of the first author, publication year, study design, sample characteristics, dietary assessment time and tools, mental health outcome measures, and other relevant information were extracted. In total, 13 articles were included in this review and assessed qualitatively. The results demonstrated that dietary intake of n-3 PUFA during pregnancy was associated with perinatal mental health, but the effect of n-3 PUFA supplementation was influenced by pre-existing medical conditions, socio-demographic characteristics, and dietary and lifestyle patterns during pregnancy. Our review found that sources of n-3 PUFA may have differential effects on woman's mental health during and after pregnancy. Further research using large-size cohort or well-controlled trial protocol is needed to determine the effect of n-3 PUFA supplementation during pregnancy on perinatal mental health.

Hepatitis B Prevalence among Men Who Have Sex with Men in Brazil.

Hepatitis B virus (HBV) is a global public health problem and requires specific prevention actions, particularly focusing on the key populations, such as men who have sex with men (MSM). We aimed at assessing the prevalence of HBV infection, among MSM, in a multicity study in Brazil. In 2016, we conducted a survey using a respondent-driven sampling methodology in 12 Brazilian cities. Rapid tests (RT) were performed on 3178 samples from those MSM. Positive results were tested for HBV DNA and sequenced. If negative for HBV DNA, samples were tested for serological markers. The prevalence rate of HBV exposure and clearance was 10.1% (95% CI: 8.1-12.6), and 1.1% (95%; CI: 0.6-2.1) were confirmed to be HBsAg-positive. Of those samples tested for anti-HBs (n = 1033), only 74.4% presented a serological profile analogous to that elicited by hepatitis B vaccination. Among HBsAg-positive samples (n = 29), 72.4% were HBV DNA-positive, and from these, 18 were sequenced. HBV genotypes A, F, and G were found in 55.5%, 38.9%, and 5.6%, respectively. This study indicates high prevalence rates of MSM HBV exposure and a low positivity index for the serological marker of HBV vaccine immunity. These findings may contribute to the discussion of strategies to prevent hepatitis B and reinforce the importance of promoting HBV vaccination in this key population.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

Aurora B Kinase Inhibition by AZD1152 Concomitant with Tumor Treating Fields Is Effective in the Treatment of Cultures from Primary and Recurrent Glioblastomas.

Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5-30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.

The impact of a drug allergy label in an internal medicine ward.

Summary: Background. Drug hypersensitivity reactions are presumably immune-mediated reactions that cause reproducible signs and/or symptoms. Overdiagnosis of drug allergy, frequently self-reported, is common and carries significant limitations. We intended to analyze the frequency and impact of drug allergy in hospitalized patients. Methods. A retrospective study was conducted in an Internal Medicine ward at a tertiary hospital in Portugal. All patients with a drug allergy report admitted within a 3-year period were included. Data were collected from their electronic medical records. Results. We found that 15.4% of patients had a report of drug allergy, with antibiotics being the most common (56.4%), followed by non-steroidal anti-inflammatory drugs (21.7%) and radiocontrast media (7.0%). The allergy report affected the clinical approach of 14.5% of patients by motivating the use of second-line agents, or the eviction of necessary procedures. The usage of alternative antibiotics entailed a cost increase of 2.4 times. There were 14.7% of patients to whom the suspected drug was administered: 87.0% tolerated and 13.0% developed a reaction. Only 1.9% were referred to our Allergy and Clinical Immunology department and proceeded in their allergy study. Conclusions. In this study, a considerable number of patients had a drug allergy label on their records. This label contributed to an increase in the cost of treatment, or the avoidance of necessary exams. However, disregarding an allergy record may lead to potentially life-threatening reactions that proper risk assessment could avoid. Further investigation should always be part of the follow-up routine of these patients, and better articulation between departments should be encouraged.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study / Manejo de las vías respiratorias en la insuficiencia respiratoria aguda SARS-COV-2: un estudio observacional prospectivo multicéntrico

Objective Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions Endotracheal Intubation Adverse Events. Main variables of interests The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent (AU)

Objetivo Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones Eventos adversos de la intubación endotraqueal. Principales variables de interés El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes (AU)

Predictors of Falls with Injuries in People with Parkinson's Disease.

Background: Falls are frequent in Parkinson's disease (PD), but there is lack of information about predictors of injurious falls. Objectives: To determine predictors of falls with injuries in people with PD; to compare circumstances and consequences of falls in single and recurrent fallers. Methods: Participants (n = 225) were assessed by disease-specific, self-report, and balance measures, and followed-up for 12 months with a diary to record falls, their circumstances, and injuries. Univariate and multivariate analyses were performed. Circumstances and consequences of falls presented by single and recurrent fallers were compared. Results: A total of 805 falls were analyzed, 107 (13%) were falls with injuries. Multivariate logistic regression model revealed that greater PD duration and higher balance confidence were protective factors; better balance during gait, outdoor falls, and falls related to extrinsic factors were risk factors for falls with injuries, when compared to falls with no injuries. Multivariate multinomial regression model revealed that, when compared to zero fall, past falls and daily levodopa equivalent dose were predictors of falls with injuries; these predictors together with disability were predictors of falls with no injuries. Single falls (n = 27; 3%) were more common outdoors because of extrinsic factors, whereas recurrent falls (n = 778; 97%) were more common indoors because of intrinsic factors. Single falls led to more injuries than recurrent falls (P < 0.05). Conclusions: Different predictors of falls with injuries were obtained when different outcomes were compared. It should be noted that falls with injuries might be influenced by fall-related activities and environmental factors. Single and recurrent falls differed on circumstances and consequences.