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Background: A short-term insulin intensive therapy is an important method used in clinical practice to control blood glucose, and a scientific post-treatment plan is key to long-term blood glucose stability control. This study aimed to investigate efficacy and safety of early conversion of intensive insulin therapy to IDegLira in T2DM patients. Methods: This study was a prospective study, involving 80 T2DM patients finally. Patients were firstly treated with insulin for intensified therapy (Pre-IDegLira group), then switched to insulin degludec and liraglutide (IDegLira) for 3 months (IDegLira-3 months group). Data including HbA1c, fasting blood glucose, fasting C-peptide, weight, insulin dosage, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed. Correlations between fasting blood glucose and other parameters were evaluated with Pearson correlation analysis. Results: IDegLira early conversion significantly reduced fasting blood glucose (p<0.001), weight (p=0.015), and insulin dosage (p=0.001) of T2DM patients compared to those of Pre-IDegLira group. HbA1c level was remarkably lower in T2DM patients underwent IDegLira early conversion compared to that in Pre-IDegLira group (p<0.001), with HbA1c <7% proportion of 73.75% (59/80). IDegLira early conversion significantly downregulated levels of TC (p<0.001), TG (p<0.001), LDL-C (p<0.001), and upregulated HDL-C level (p=0.017) of T2DM patients, compared to those in Pre-IDegLira group. IDegLira early conversion markedly reduced ALT (p<0.001) and AST (p=0.002) levels of T2DM patients compared to those in Pre-IDegLira group. IDegLira early conversion demonstrated a positive correlation between fasting blood glucose and HbA1c (r=0.531, p<0.001) or TG level (r=0.336, p=0.002) in T2DM patients. Conclusion: Early conversion of intensive insulin therapy to IDegLira effectively reduced fasting blood glucose and HbA1c in T2DM patients with higher safety.

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The anti-cancer mechanism of High-dose Vitamin C (HDVC) is mainly to participate in the Fenton reaction, hydroxylation reaction, and epigenetic modification, which leads to the energy crisis, metabolic collapse, and severe peroxidation stress that results in the proliferation inhibition or death of cancer cells. However, the mainstream view is that HDVC does not significantly improve cancer treatment outcomes. In clinical work and scientific research, we found that some drugs or therapies can significantly improve the anti-cancer effects of HDVC, such as PD-1 inhibitors that can increase the anti-cancer effects of cancerous HDVC by nearly three times. Here, the adjuvant and intensive therapy and synergistic mechanisms including HDVC combined application of chemoradiotherapies multi-vitamins, targeted drugs, immunotherapies, and oncolytic virus are discussed in detail. Adjuvant and intensive therapy of HDVC can significantly improve the therapeutic effect of HDVC in the metabolic treatment of cancer, but more clinical evidence is needed to support its clinical application.

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PURPOSE: The purpose of this study was to assess the long-term stability of objective and subjective psychosocial improvements and fluency more than 10 years after participation in an intensive stuttering therapy camp. METHOD: Ten former participants in intensive stuttering therapy (IST; mean age at time of intervention 14; 2 years) participated in this study. Outcomes of the IST at that time were assessed with the Stuttering Severity Instrument (SSI-3; Riley, 1994) and a questionnaire to measure the psychosocial impact of stuttering. A semi-structured video call and a general questionnaire for the long-term evaluation were used to gauge the participants' perceptions of the IST. These follow-up data were compared to the therapy outcomes reported by Cook (2011, 2013). RESULT: Therapy effects on the severity of stuttering and psychosocial impact were stable over the follow-up period of more than 10 years. Moreover, scores for psychosocial impact and severity of stuttering further decreased from the end of the IST to the long-term evaluation. The intensive time and the periodically offered follow-up treatments were described as particularly positive by the participants. CONCLUSION: Intensive stuttering therapy in childhood or adolescence can have a long-term positive effect on both internal and external stuttering symptoms.

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Background and Objective: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) is the most prevalent subtype of all BCs. The primary treatment modality is endocrine therapy (ET). Traditional adjuvant ET for early-stage breast cancer (EBC) has undergone extensive exploration and is relatively well-established. However, patients at high risk of recurrence may still experience early relapse, necessitating consideration of intensified adjuvant ET to reduce recurrence risk. The objective of this narrative review is to examine various strategies for intensifying adjuvant ET in EBC, thoroughly analyze key clinical studies, and summarize the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation. Methods: As of March 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Baidu Scholar, ClinicalTrials.gov, and relevant academic conferences. Key Content and Findings: There are numerous methods to intensify adjuvant ET: (I) combining ovarian function suppression (OFS) to reduce estrogen levels in the body and induce a state of artificial menopause to enhance the efficacy of ET; (II) individual extension of the duration of ET based on patients' varying risks of recurrence, with high-risk patients covering two peak recurrence periods; (III) the addition of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) can significantly extend invasive disease-free survival and reduce the risk of recurrence, serving as the main intensive treatment for high-risk patients; (IV) combination with bone-modifying drugs (BMD) can significantly reduce rates of bone metastasis and slightly enhance prognosis but is not commonly used in adjuvant settings; (V) combined with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, current studies only show a trend towards benefit in HR+ patients with germline BRCA1/2 mutations; more data are still needed to support its clinical benefit. This narrative review examines various strategies for intensifying adjuvant ET in EBC, critically evaluates key clinical studies, and summarizes the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation. Conclusions: In the context where traditional adjuvant ET is relatively well-established, the emergence of novel ET has notably addressed issues of endocrine resistance more effectively. Various intensified adjuvant ET has shown potential in further reducing recurrence risk among high-risk patients. However, additional research and time are essential to determine the optimal approaches for intensified adjuvant ET.

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Introducción: el SARS-CoV-2 desde el 2020 generó innumerables desafíos. El decúbito prono se utilizó para mejorar la oxigenación, y la terapia nutricional se adaptó para cubrir los requerimientos y reducir complicaciones. Objetivos: evaluar la tolerancia de la nutrición enteral y su adecuación energética en pacientes ventilados en decúbito prono con infección por SARS-CoV-2, en sala respiratoria del Departamento de Cuidados Intensivos Adultos del Hospital de Clínicas-Facultad de Ciencias Médicas - Universidad Nacional de Asunción, de marzo a julio 2021. Metodología: estudio observacional, descriptivo, retrospectivo, de corte transversal, de casos consecutivos, con información obtenida de fichas de pacientes de terapia intensiva, que recibieron soporte nutricional en posición prona. Se tomaron datos demográficos, clínicos y nutricionales. Se evaluó la tolerancia nutricional durante la posición prona, definiéndola como la presencia de un volumen de residuo gástrico < 500 mL cada 6 h.. La adecuación energética fue determinada teniendo en cuenta el porcentaje cumplido de la prescripción nutricional. Resultados: se reclutaron 41 pacientes. El 60,9 % eran hombres; la mediana de edad fue 55 años (RIC=23). Las principales comorbilidades fueron obesidad (57,3 %) e hipertensión arterial (43,9 %). El 85,4 % presentó buena tolerancia gástrica en posición prono, con residuo gástrico menor a 500 ml. El porcentaje de adecuación energética fue de 84 %. Conclusión: la terapia nutricional enteral en decúbito prono fue bien tolerada por la mayoría de nuestros pacientes, posibilitando alcanzar los requerimientos nutricionales indicados.

Introduction: SARS-CoV-2 since 2020 has generated countless challenges. Prone position was used to improve oxygenation, and nutritional therapy was adapted to meet requirements and reduce complications. Objectives: evaluate the tolerance of enteral nutrition and its energetic adequacy in ventilated patients in the prone position with SARS-CoV-2 infection, in the respiratory room of the Adult Intensive Care Department of the Hospital de Clínicas - Facultad de Ciencias Médicas - Universidad Nacional de Asunción, from March to July 2021. Methodology: observational, descriptive, retrospective, cross-sectional study of consecutive cases, with information obtained from records of intensive care patients, who received nutritional support in a prone position. Demographic, clinical and nutritional data were taken. Nutritional tolerance was evaluated during the prone position, defining it as the presence of a volume of gastric residue < 500 mL every 6 h. Energy adequacy was determined taking into account the percentage fulfilled of the nutritional prescription. Results: 41 patients were recruited. 60.9 % were men; the median age was 55 years (IQR=23). The main comorbidities were obesity (57.3 %) and high blood pressure (43.9 %). 85.4 % had good gastric tolerance in the prone position, with gastric residue less than 500 ml. The percentage of energy adequacy was 84 %. Conclusion: enteral nutritional therapy in the prone position was well tolerated by the majority of our patients, making it possible to achieve the indicated nutritional requirements.

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We conducted a phase I trial in newly diagnosed acute myeloid leukaemia (AML) to investigate the combination of two novel targeted agents, gemtuzumab ozogamicin (GO) and midostaurin, with intensive chemotherapy in FLT3-mutated AML and CBF leukaemia. Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

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Intensive insulin therapy has been extensively used to control blood glucose levels because of its ability to reduce the risk of chronic complications of diabetes. According to current guidelines, intensive glycemic control requires individualized glucose goals rather than as low as possible. During intensive therapy, rapid blood glucose reduction can aggravate microvascular and macrovascular complications, and prolonged overuse of insulin can lead to treatment-induced neuropathy and retinopathy, hypoglycemia, obesity, lipodystrophy, and insulin antibody syndrome. Therefore, we need to develop individualized hypoglycemic plans for patients with diabetes, including the time required for blood glucose normalization and the duration of intensive insulin therapy, which deserves further study.

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BACKGROUND: Children with Developmental Coordination Disorder (DCD) often (<87 %) experience postural control problems, impacting all levels of the International Classification of Functioning, Disability and Health (ICF) including their daily participation, self-esteem and mental health. Due to the multisystemic nature of postural control, comprehensive therapy should target all systems which is currently not the case. Highly intensive therapy is effective and commonly used in pediatric populations, but has not been explored yet to train postural control in children with DCD. AIMS: To investigate the effects of a highly intensive functional balance therapy camp at all ICF levels in children with DCD. METHODS AND PROCEDURES: The effects on postural control, muscle activity, brain alterations, self-perceived competence, self-identified goals, gross motor activities and participation are evaluated. Participants are assessed pre- and post-intervention, including a 3 months follow-up. Forty-eight children with DCD, aged 6-12 years old, receive 40 h of comprehensive balance training. This intervention is fun, individually tailored, targets all postural control systems, implements different motor learning strategies and includes both individual and group activities. CONCLUSION: Novel insights into the effects of a highly intensive comprehensive balance therapy camp designed for children with DCD will be gained at all levels of the ICF.

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INTRODUCTION: Type 2 diabetes is a widespread health concern with significant implications for patient well-being. Poor glycaemic control can lead to long-term complications, hypoglycaemia and glycaemic variability, highlighting the importance of setting treatment goals. This podcast, "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting", introduces non-intensive insulin treatment and continuous glucose monitoring (CGM) as crucial tools in achieving these goals. OBJECTIVES AND RATIONALE: The advantages of CGM over blood glucose monitoring (BGM) are explored, emphasizing its real-time glucose data provision and how it empowers patients to make informed treatment decisions. Drawing on randomized controlled trials (RCTs), the compelling evidence of CGM's effectiveness in patients with type 2 diabetes on basal insulin treatment are discussed. Additionally, the real-world evidence, comparing outcomes between insulin-treated and non-insulin-treated patients are also addressed. The podcast examines the link between glycaemic control and acute complications requiring hospitalizations and how CGM contributes to a better quality of life for patients with type 2 diabetes. Empowering patients is central to this podcast, with a focus on education, engagement and strategies for integrating CGM data into treatment plans. The pivotal role of healthcare providers in supporting patients on non-intensive insulin treatment and CGM in the primary care setting is addressed. Addressing challenges and barriers in CGM adoption, including cost considerations, technology accessibility and patient concerns, is vital to its widespread use. There is also a consideration of the cost-effectiveness of CGM in type 2 diabetes management. The podcast provides insights into when to consider CGM, including intermittent use and data integration with other health technologies. It emphasizes the potential for improved patient outcomes and a reduced burden of type 2 diabetes. Practical tips for interpreting the Ambulatory Glucose Profile (AGP) report are shared, benefitting primary care healthcare professionals new to CGM. CONCLUSION: The podcast "The use of CGM in optimizing type 2 diabetes management with non-intensive insulin treatment in the primary care setting" highlights the transformative potential of CGM in type 2 diabetes care. It encourages patients and healthcare providers to consider CGM as an integral part of treatment plans, ultimately improving the lives of those living with type 2 diabetes. Podcast Video (MP4 261831 KB).

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BACKGROUND: Pediatric stroke is a rare medical condition that often leads to long-lasting motor and cognitive impairments. Although therapies for adults after a stroke are well described, treatments for motor deficits following a pediatric stroke are yet to be investigated. We report a case of pediatric stroke in the chronic phase, in which a combination of novel treatments resulted in a significant improvement in physical function. CASE REPORT: A seven-year-old girl with a left hemispheric cerebral infarction lost almost all right upper extremity motor function. Following onabotulinumtoxinA treatment, she underwent hand-arm bimanual intensive therapy augmented with a hybrid assistive limb for 90 h over 15 days. Evaluation after the training revealed significant improvements in physical function, daily activities, and occupational performance. CONCLUSIONS: This report highlights the importance of innovative combinations of techniques in the treatment of pediatric stroke.

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BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION: Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.

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ABSTRACT BACKGROUND: Acute kidney failure is a serious consequence of coronavirus disease 2019 (COVID-19). OBJECTIVES: To identify the prevalence of COVID-19, kidney failure, frequency of death, and associated factors in patients receiving intensive care. DESIGN AND SETTING: Analytical cross-sectional study conducted in the intensive care unit (ICU) of a medium-sized philanthropic general hospital in center-west Minas Gerais. METHODS: Adults and older individuals who underwent real-time polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated by the nephrology team. RESULTS: Among the 176 patients, the prevalence of COVID-19 and acute kidney injury (AKI) were 103 (58.5%) and 132 (75%), respectively, and 44 (25%) had chronic kidney disease (CKD) and 16 (15,5%) were positive for SARS-CoV-2. In the Charlson index classification, which estimates the risk of death, a statistically significant difference was identified in the percentages of groups with and without COVID-19 for indices 0, 1, and 2. There was a significant association between kidney disease and ICU mortality (P < 0.05). Patients with CKD had fewer fatal outcomes (13/97, 13.4%) than those with AKI (85/97, 87.6%). CONCLUSIONS: COVID-19 rates remained high long after diagnosis and prevention of SARS-CoV-2 infection. In addition, a higher death rate among patients who developed AKI, whose prevalence was also greater than that in the national literature, regardless of the presence of COVID-19, revealed a worrying scenario and corroborated the need for early and judicious approaches to preserve the lives of patients with AKI admitted to intensive care units.

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This narrative review article explores the current scientific knowledge on the definition, epidemiology, diagnostic criteria, microbiology, treatment, and prevention of severe community-acquired pneumonia (SCAP) in immunocompetent adults. At present, despite major scientific advances in diagnostic evaluation, clinical management, antimicrobial therapy, and prevention, severe community-acquired pneumonia remains a major cause of morbidity and mortality, as well as having a major economic impact in terms of increased healthcare expenditure worldwide. This pathology is considered one of the leading causes of sepsis/septic shock, with an extremely high overall mortality rate, which justifies all the effort in early diagnosis, proper management, and prompt initiation of antimicrobial therapy. Including biomarkers (isolated or in combination) associated with applying diagnostic criteria and prognostic severity scales in clinical practice helps identify patients with severe community-acquired pneumonia, defines immediate admission to the intensive care unit, and, thus, minimizes the adverse outcomes of this serious pathology.

Este artículo de revisión narrativa tiene como objetivo explorar el conocimiento actual disponible basado en datos científicos respeto a la definición, la epidemiología, los criterios diagnósticos, la microbiología, el tratamiento y la prevención de la neumonía grave adquirida en la comunidad) en individuos adultos inmunocompetentes. En la actualidad, pese a los grandes avances científicos obtenidos en la evaluación diagnóstica, el manejo clínico, la terapia antimicrobiana y la prevención, la neumonía grave adquirida en la comunidad sigue siendo una causa importante de morbilidad y mortalidad, además de producir un gran impacto económico con la elevación de los costes sanitarios en todo el mundo. Esta patología es considerada una de las principales causas de sepsis/choque séptico, con una tasa de mortalidad global extremadamente elevada, lo que justifica todo el esfuerzo en el diagnóstico precoz, el manejo en un ambiente adecuado y el inicio temprano y apropiado de la terapia antimicrobiana. La inclusión de biomarcadores (aislados o en combinación) asociada a la aplicación de los criterios diagnósticos y escalas pronósticas de gravedad en la práctica clínica, sirven para identificar a los pacientes con neumonía adquirida en la comunidad grave, definir el ingreso inmediato en la unidad de cuidados intensivos y, de esta forma, minimizar los resultados negativos de esta grave patología.

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Este artículo de revisión narrativa tiene como objetivo explorar el conocimiento actual disponible basado en datos científicos respeto a la definición, la epidemiología, los criterios diagnósticos, la microbiología, el tratamiento y la prevención de la neumonía grave adquirida en la comunidad) en individuos adultos inmunocompetentes. En la actualidad, pese a los grandes avances científicos obtenidos en la evaluación diagnóstica, el manejo clínico, la terapia antimicrobiana y la prevención, la neumonía grave adquirida en la comunidad sigue siendo una causa importante de morbilidad y mortalidad, además de producir un gran impacto económico con la elevación de los costes sanitarios en todo el mundo. Esta patología es considerada una de las principales causas de sepsis/choque séptico, con una tasa de mortalidad global extremadamente elevada, lo que justifica todo el esfuerzo en el diagnóstico precoz, el manejo en un ambiente adecuado y el inicio temprano y apropiado de la terapia antimicrobiana. La inclusión de biomarcadores (aislados o en combinación) asociada a la aplicación de los criterios diagnósticos y escalas pronósticas de gravedad en la práctica clínica, sirven para identificar a los pacientes con neumonía adquirida en la comunidad grave, definir el ingreso inmediato en la unidad de cuidados intensivos y, de esta forma, minimizar los resultados negativos de esta grave patología.

his narrative review article explores the current scientific knowledge on the definition, epidemiology, diagnostic criteria, microbiology, treatment, and prevention of severe community-acquired pneumonia (SCAP) in immunocompetent adults. At present, despite major scientific advances in diagnostic evaluation, clinical management, antimicrobial therapy, and prevention, severe community-acquired pneumonia remains a major cause of morbidity and mortality, as well as having a major economic impact in terms of increased healthcare expenditure worldwide. This pathology is considered one of the leading causes of sepsis/septic shock, with an extremely high overall mortality rate, which justifies all the effort in early diagnosis, proper management, and prompt initiation of antimicrobial therapy. Including biomarkers (isolated or in combination) associated with applying diagnostic criteria and prognostic severity scales in clinical practice helps identify patients with severe community-acquired pneumonia, defines immediate admission to the intensive care unit, and, thus, minimizes the adverse outcomes of this serious pathology.

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This is a report on an outbreak of Panton-Valentine leucocidin-producing meticillin-resistant Staphylococcus aureus (PVL-MRSA) in an intensive care unit (ICU) during the COVID-19 pandemic that affected seven patients and a member of staff. Six patients were infected over a period of ten months on ICU by the same strain of PVL-MRSA, and a historic case identified outside of the ICU. All cases were linked to a healthcare worker (HCW) who was colonized with the organism. Failed topical decolonization therapy, without systemic antibiotic therapy, resulted in ongoing transmission and one preventable acquisition of PVL-MRSA. The outbreak identifies the support that may be needed for HCWs implicated in outbreaks. It also demonstrates the role of whole-genome sequencing in identifying dispersed and historic cases related to the outbreak, which in turn aids decision-making in outbreak management and HCW support. This report also includes a review of literature of PVL-MRSA-associated outbreaks in healthcare and highlights the need for review of current national guidance in the management of HCWs' decolonization regimen and return-to-work recommendations in such outbreaks.

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Background: Despite children and young people (CYP) having a low risk for severe coronavirus disease 2019 (COVID-19) outcomes, there is still a degree of uncertainty related to their risk in the context of immunodeficiency or immunosuppression, primarily due to significant reporting bias in most studies, as CYP characteristically experience milder or asymptomatic COVID-19 infection and the severe outcomes tend to be overestimated. Methods: A comprehensive systematic review to identify globally relevant studies in immunosuppressed CYP and CYP in general population (defined as younger than 25 years of age) up to 31 October 2021 (to exclude vaccinated populations) was performed. Studies were included if they reported the two primary outcomes of our study, admission to intensive therapy unit (ITU) and mortality, while data on other outcomes, such as hospitalization and need for mechanical ventilation were also collected. A meta-analysis estimated the pooled proportion for each severe COVID-19 outcome, using the inverse variance method. Random effects models were used to account for interstudy heterogeneity. Findings: The systematic review identified 30 eligible studies for each of the two populations investigated: immunosuppressed CYP (n = 793) and CYP in general population (n = 102,022). Our meta-analysis found higher estimated prevalence for hospitalization (46% vs. 16%), ITU admission (12% vs. 2%), mechanical ventilation (8% vs. 1%), and increased mortality due to severe COVID-19 infection (6.5% vs. 0.2%) in immunocompromised CYP compared with CYP in general population. This shows an overall trend for more severe outcomes of COVID-19 infection in immunocompromised CYP, similar to adult studies. Interpretation: This is the only up-to-date meta-analysis in immunocompromised CYP with high global relevance, which excluded reports from hospitalized cohorts alone and included 35% studies from low- and middle-income countries. Future research is required to characterize individual subgroups of immunocompromised patients, as well as impact of vaccination on severe COVID-19 outcomes. Systematic Review Registration: PROSPERO identifier, CRD42021278598.

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Objective: The terms critical care and the Intensive Care Unit (ICU) are often used interchangeably to describe a place of care. Defining critical care becomes challenging because of the colloquial use of the term. Using concept analysis allows for the development of definition and meaning. The aim of this concept analysis is to distinguish the use of the term critical care to develop an operational definition which describes what constitutes critical care. Method: Walker and Avant's eight-step approach to concept analysis guided this study. Five databases (CINAHL, Scopus, PubMed, ProQuest Dissertation Abstracts and Medline in EBSCO) were searched for studies related to critical care. The search included both qualitative and quantitative studies written in English and published between 1990 and 2022. Results: Of the 439 papers retrieved, 47 met the inclusion criteria. The defining attributes of critical care included 1) a maladaptive response to illness/injury, 2) admission modelling criteria, 3) advanced medical technologies, and 4) specialised health professionals. Antecedents were associated with illness/injury that progressed to a level of criticality with a significant decline in both physical and psychological functioning. Consequences were identified as either death or survival with/without experiencing post-ICU syndrome. Conclusion: Describing critical care is often challenging because of the highly technical nature of the environment. This conceptual understanding and operational definition will inform future research as to the scope of critical care and allow for the design of robust evaluative instruments to better understand the nature of care in the intensive care environment.

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Intensive therapies have become increasingly popular for children with hemiparesis in the last two decades and are specifically recommended because of high levels of scientific evidence associated with them, including multiple randomized controlled trials and systematic reviews. Common features of most intensive therapies that have documented efficacy include: high dosages of therapy hours; active engagement of the child; individualized goal-directed activities; and the systematic application of operant conditioning techniques to elicit and progress skills with an emphasis on success-oriented play. However, the scientific protocols have not resulted in guiding principles designed to aid clinicians with understanding the complexity of applying these principles to a heterogeneous clinical population, nor have we gathered sufficient clinical data using intensive therapies to justify their widespread clinical use beyond hemiparesis. We define a framework for describing moment-by-moment therapeutic interactions that we have used to train therapists across multiple clinical trials in implementing intensive therapy protocols. We also document outcomes from the use of this framework during intensive therapies provided clinically to children (7 months-20 years) from a wide array of diagnoses that present with motor impairments, including hemiparesis and quadriparesis. Results indicate that children from a wide array of diagnostic categories demonstrated functional improvements.

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Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n = 633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n = 3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

In this study we performed a real-world data analysis of treatment for advanced colorectal cancer that had spread to other parts of patients' bodies, by investigating the medical records of 4462 patients. We wanted to see how well different treatments worked and what kinds of patients received them. We found that the most important factors when choosing between different treatments were the patient's age and how well they could perform their everyday tasks. We found that using specialized medicines in the intensive treatment group, and a drug called bevacizumab in the less intensive group, resulted in better patient outcomes.

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Children with Unilateral Spastic Cerebral Palsy (US CP) have motor and somatosensory impairments that affect one side of their body, impacting upper limb functioning. These impairments contribute negatively to children's bimanual performance and quality of life. Intensive home-based therapies have been developed and have demonstrated their feasibility for children with US CP and their parents, especially when therapies are designed with the proper coaching of families. Mirror Therapy (MT) is being studied to become an approachable intensive and home-based therapy suitable for children with US CP. The aim of this study is to analyze the feasibility of a five-week home-based program of MT for children with US CP that includes coaching by the therapist. Six children aged 8-12 years old performed the therapy for five days per week, 30 min per day. A minimum of 80% of compliance was required. The feasibility included compliance evaluations, total dosage, perceived difficulty of the exercises, and losses of follow-ups. All children completed the therapy and were included in the analysis. The total accomplishment was 86.47 ± 7.67. The perceived difficulty of the exercises ranged from 2.37 to 4.51 out of 10. In conclusion, a home-based program of Mirror Therapy is a safe, cost-efficient, and feasible therapy for children with US CP when the therapist is involved as a coach during the entire program.