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1.
N Engl J Med ; 388(21): 1966-1980, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37224198

ABSTRACT

BACKGROUND: Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease. METHODS: In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]). RESULTS: A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib. CONCLUSIONS: Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).


Subject(s)
Crohn Disease , Janus Kinase Inhibitors , Humans , Crohn Disease/complications , Crohn Disease/drug therapy , Herpes Zoster/chemically induced , Herpes Zoster/etiology , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Janus Kinase Inhibitors/administration & dosage , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Neutropenia/chemically induced , Neutropenia/etiology , Induction Chemotherapy/adverse effects , Induction Chemotherapy/methods , Maintenance Chemotherapy/adverse effects , Maintenance Chemotherapy/methods
2.
Article in English | MEDLINE | ID: mdl-38492903

ABSTRACT

BACKGROUND & AIMS: Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy. METHODS: This post hoc analysis included pooled data from 2 phase 3, multicenter, double-blind, 12-week induction trials (U-EXCEL and U-EXCEED) and 1 maintenance trial (U-ENDURE). Daily diary data for the first 15 days of UPA45 or placebo (PBO) treatment were used to analyze improvement in very soft/liquid stool frequency (SF) and abdominal pain score (APS). Clinical outcomes were evaluated at every study visit. RESULTS: Overall, 1021 patients (n = 674 UPA45; n = 347 PBO) were analyzed. UPA45 demonstrated greater efficacy vs PBO for SF <3 and APS ≤1, providing rapid relief by day 5 or 6, regardless of prior biologic exposure. Mean changes in SF and APS were greater with UPA45 beginning at week 2 (-2.0 and -0.5, respectively; P < .001) and were maintained through week 12 (-3.0 and -1.0, respectively; P < .001) vs PBO. The first achievement of daily SF/APS clinical remission occurred earlier with UPA45 (median, 13 d) vs PBO (median, 32 d), and patients treated with UPA45 showed improved rates of SF/APS clinical remission (21.1% UPA45 vs 8.9% PBO) and clinical response (58.8% UPA45 vs 37.9% PBO) starting at week 2 (both P ≤ .01). CONCLUSIONS: UPA45 provided rapid relief of clinical symptoms within the first week of treatment in patients with CD. CLINICALTRIALS: gov numbers: NCT03345849, NCT03345836, and NCT03345823.

3.
Article in English | MEDLINE | ID: mdl-38492904

ABSTRACT

BACKGROUND & AIMS: Upadacitinib, an oral Janus kinase inhibitor, achieved significantly higher rates of clinical remission and endoscopic response vs placebo during induction (U-EXCEL [NCT03345849], U-EXCEED [NCT03345836]) and maintenance (U-ENDURE [NCT03345823]) treatment in patients with moderate-to-severe Crohn's disease. Prior biologic failure is often associated with reduced responses to subsequent therapies. This post hoc analysis assessed upadacitinib efficacy by prior biologic failure status. METHODS: Patients were randomized to placebo or upadacitinib 45 mg (UPA45) for 12 weeks (induction). UPA45 clinical responders were enrolled in U-ENDURE and rerandomized to placebo, upadacitinib 15 mg, or upadacitinib 30 mg (UPA30) for 52 weeks. Assessments were by prior biologic failure. RESULTS: Of 1021 patients, 733 (71.8%) had prior biologic failure. Across outcomes and subgroups, upadacitinib-treated patients achieved higher rates vs placebo. During induction, upadacitinib had higher rates vs placebo for clinical remission based on stool frequency/abdominal pain score (without failure: 54.0% vs 28.3%; with failure: 42.2% vs 14.1%) and endoscopic response (without failure: 52.0% vs 16.2%; with failure: 35.7% vs 5.3%). In maintenance, the greatest treatment effect (upadacitinib vs placebo) was among patients with prior biologic failure treated with UPA30 (clinical remission without failure: 58.5% vs 32.7%; with failure: 42.5% vs 8.7%; endoscopic response without failure: 43.9% vs 17.9%; with failure: 38.9% vs 4.0%). Patients without vs with prior biologic failure had fewer adverse events. CONCLUSIONS: Upadacitinib led to higher absolutes rates of clinical and endoscopic outcomes in patients without vs with prior biologic failure. Patients treated with upadacitinib achieved greater rates of clinical and endoscopic improvements vs placebo, regardless of prior biologic exposure. CLINICALTRIALS: gov: NCT03345849, NCT03345836, NCT03345823.

4.
Cytokine ; 176: 156512, 2024 04.
Article in English | MEDLINE | ID: mdl-38281360

ABSTRACT

Complex inflammatory crosstalk between muscular and adipose organs during ageing is controlled by adipokines and myokines. The Adiponectin/Leptin ratio (A/L ratio) has proven to be a promising biomarker for identifying insulin sensitivity, cardiovascular risk and adipose tissue inflammation. Although the A/L ratio has been related to inflammatory conditions, its ability to associate with or indicate the behavior of other inflammatory mediators remains unknown. The present study aimed to verify the association between the A/L ratio and a panel of inflammatory biomarkers in community-dwelling older women. The plasmatic concentrations of adiponectin, leptin, resistin, brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukins 2, 4, 5, 6, 8 and 10, tumour necrosis factor (TNF) and its soluble receptors (sTNF-r) 1 and 2 were evaluated in 71 community-dwelling older women with 75 (±7) years. The A/L ratio was negative and inverse correlated with BNDF (r = -0.29; p = 0.01), IL-8 (r = -0.37; p = 0.001) and sTNFr- 1 (r = -0.98; p < 0.001) levels. A strong and inverse association, with proportional effect, between A/L ratio and sTNFr-1 concentrations was found (Adjusted R2 = 0.22; ß = -0.48; p > 0.001). It suggests that the presence of sTNFr-1 causes an inflammatory effect that affect cross-talk between muscle and adipose tissue, contributing to pro-inflammatory imbalance, which may have molecular and functional consequences. In addition, we provide insights into diagnostic biomarkers for inflammation, especially related to muscle wasting and intrinsic capacity in older people.


Subject(s)
Adiponectin , Leptin , Humans , Female , Aged , Resistin , Biomarkers , Inflammation , Tumor Necrosis Factor-alpha
5.
Trop Med Int Health ; 29(1): 6-12, 2024 01.
Article in English | MEDLINE | ID: mdl-37952931

ABSTRACT

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.


Subject(s)
Chagas Cardiomyopathy , Heart Failure , Humans , Quality of Life/psychology , Chagas Cardiomyopathy/complications , Stroke Volume , Ventricular Function, Left , Surveys and Questionnaires
6.
Neurourol Urodyn ; 43(3): 672-679, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38247352

ABSTRACT

AIMS: To investigate the frequency and the factors associated with urinary incontinence (UI) in a sample of middle-aged and older women with lower limb osteoarthritis (OA). METHODS: Women aged 50 years or older with clinical hip/knee OA diagnoses were recruited for this cross-sectional study. Self-reported UI and type, sociodemographic characteristics, medical conditions, physical activity level, anthropometric and body composition measurements, muscle strength, and physical function were assessed. Uni and multivariable logistic regression were used to investigate the factors associated with UI. RESULTS: Among 100 middle-aged and older women (mean 67.27 ± 8.77 SD years), 67% reported UI. In the UI group, 33% reported stress UI, 36% reported urgency UI, and 31% reported mixed UI. In the univariate analysis, age, level of physical activity, pulmonary disease, number of medications, body mass index (BMI), number of deliveries, and activity limitation were significantly associated with UI. In the multivariable analysis, older age (60-69 years OR: 4.91, 95% CI: 1.25-19.36; ≥70 years OR: 8.06, 95% CI: 1.96-33.22), compared to 50-59 years, morbid obesity (OR: 14.10, 95% CI: 1.36-146.48), compared to BMI < 30 kg/m2 , and activity limitation (OR: 5.31, 95% CI: 1.61-17.54), assessed as short physical performance battery ≤8, remained significantly associated with UI. CONCLUSIONS: UI was highly frequent among middle-aged and older women with hip/knee OA. Older age, activity limitation, and morbid obesity were independently associated with UI. Interventions targeting physical function and weight management must be considered to prevent and treat UI in this population.


Subject(s)
Obesity, Morbid , Osteoarthritis, Hip , Osteoarthritis, Knee , Urinary Incontinence, Stress , Urinary Incontinence , Middle Aged , Humans , Female , Aged , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/epidemiology , Cross-Sectional Studies , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/epidemiology , Obesity, Morbid/complications , Outpatients , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology , Risk Factors , Urinary Incontinence, Stress/complications , Prevalence
7.
J Ren Nutr ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38914380

ABSTRACT

OBJECTIVE: To assess the association of residual diuresis with sarcopenia in patients with Chronic Kidney Disease (CKD) on hemodialysis. METHODS: Through a cross-sectional study, patients on hemodialysis were subjected to a Dual Energy Radiologic Absorption (DEXA) exam to record muscle mass. Based on the volume of urine collected in 24 hours, patients were classified as anuric (diuresis ≤ 100 mL/day) or non-anuric (diuresis > 100 mL/day). Functional performance was evaluated by Short Physical Performance Battery (SPPB) and muscle strength by handgrip strength and 5-repetition sit-to-stand test. The association between the absence of residual urine and the presence of sarcopenia, low SPPB, and low muscle strength was analyzed using a binary logistic regression model. RESULTS: Ninety-two patients, with a mean age of 54.4 years (95% CI 51.3 - 57.4) and with a mean diuresis volume of 476.3 mL/day (95% CI 320.4 - 632.2) were evaluated (48 anuric and 44 non-anuric). Anuric patients had a 2.77 (95% CI 1.14 - 6.73) times greater probability of sarcopenia and had a 3.55 (1.14 - 11.0) times greater probability of low SPPB, regardless of gender, age, and time on dialysis. Gender was the other associated variable for the presence of sarcopenia, with males having a 3.30 (95% CI 1.34 - 8.13) times higher risk. There were no associations with muscle strength. CONCLUSION: The absence of residual diuresis in patients on hemodialysis is associated with a higher risk of sarcopenia and low functional performance.

8.
J Aging Phys Act ; 32(2): 225-235, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38134899

ABSTRACT

Knowledge of how the different types of sedentary behaviors (SB) are associated with functional limitations can guide professionals who work with older adults on better recommendations about the amount of daily time that should be encouraged in each type of SB. The objective was to estimate the associations between two SB typologies (SB television [TV] and SB computer/internet) and the presence of handgrip strength, lower limb strength, gait speed, and balance limitations in Brazilian community-dwelling older adults. This is a cross-sectional study with 1,298 community-dwelling older adults (≥60 years). SB was assessed by self-reporting daily time spent watching TV or using computer/internet (categorized into <2, 3-4, and ≥5 hr/day). Outcomes were handgrip strength, lower limb strength, gait speed, and balance limitations considering referenced cutoff points. Older adults in SB TV ≥5 hr/day had 1.75 (95% confidence interval [CI] [1.07, 2.86]) and 1.88 (95% CI [1.02, 3.46]) times more chances of handgrip strength and gait speed limitations, respectively. On the other hand, those who spent 3-4 and ≥5 hr/day in SB computer/internet had 0.45 (95% CI [0.20, 0.99]) and 0.37 (95% CI [0.15, 0.93]) had less chances of lower limb strength and balance limitations, respectively. In conclusion, functional limitations would be associated differently depending on the type of SB in the older adults sampled.


Subject(s)
Sedentary Behavior , Walking Speed , Humans , Aged , Walking Speed/physiology , Hand Strength , Independent Living , Cross-Sectional Studies , Muscle Strength/physiology
9.
J Neural Transm (Vienna) ; 130(1): 65-76, 2023 01.
Article in English | MEDLINE | ID: mdl-36401748

ABSTRACT

Access to environmental opportunities can favor children's learning and cognitive development. The objectives is to construct an index that synthesizes environmental learning opportunities for preschoolers considering the home environment and verify whether the index can predict preschoolers' cognitive development. A quantitative, cross-sectional, exploratory study was conducted with 51 preschoolers using a multi-attribute utility theory (MAUT). The criteria used for drawing up the index were supported by the literature and subdivided in Group A "Resources from the house" extracted from HOME Inventory including: (1) to have three or more puzzles; (2) have at least ten children's books; (3) be encouraged to learn the alphabet; (4) take the family out at least every 2 weeks. Group B "Screens" (5) caution with using television; (6) total screen time in day/minutes. Group C "Parental Schooling" (7) maternal and paternal education. Pearson correlation analyses and univariate linear regression were performed to verify the relationship between the established index with cognitive test results. The index correlated with the total score of the mini-mental state exam (MMC) and verbal fluency test (VF) in the category of total word production and word production without errors. Multicriteria index explained 18% of the VF (total word production), 19% of the VF (total production of words without errors) and 17% of the MMC. The present multicriteria index has potential application as it synthesizes the preschooler's environmental learning opportunities and predicts domains of child cognitive development.


Subject(s)
Cognition , Learning , Child , Humans , Cross-Sectional Studies
10.
Pediatr Blood Cancer ; 70(10): e30561, 2023 10.
Article in English | MEDLINE | ID: mdl-37430425

ABSTRACT

Paediatric palliative care aims to support children and young people with life-limiting or life-threatening conditions, and their families, from the time of diagnosis. Early integration within oncology has been recognised as having benefits for all involved, whatever the outcome may be. Through improved communication and advance care planning, it enables user-centred care, where concerns about quality of life, preferences and values are given the same relevance as cutting-edge therapy. Challenges to the integration of palliative care within paediatric oncology include raising awareness and providing education, whilst searching for the best care model and adapting to an ever-changing therapeutic scenario.


Subject(s)
Advance Care Planning , Neoplasms , Child , Humans , Adolescent , Palliative Care , Quality of Life , Medical Oncology , Neoplasms/diagnosis , Neoplasms/therapy
11.
BMC Public Health ; 23(1): 2353, 2023 11 28.
Article in English | MEDLINE | ID: mdl-38017390

ABSTRACT

BACKGROUND: Although it is well known that obesity is frequently associated with reduced levels of habitual physical activity (HPA), which contributes to determining severe oxidative stress and inflammatory state, this association is however unknown in preschoolers so far. This study aimed to investigate the association between biomarkers of redox status and cytokines with different patterns of HPA according to the adiposity of preschoolers. METHODS: A cross-sectional study was conducted in 50 preschoolers (25 overweight/obese, OW/OB and 25 eutrophic, EU), matched for age, sex, economic level, and maternal education. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activities, substances reactive to thiobarbituric acid (TBARS), soluble tumor necrosis factor receptors (sTNFRs), and leptin levels were evaluated. HPA levels were evaluated by accelerometry (ActiGraph GT9X accelerometer). Correlation, multiple linear regression, and partial least squares regression analysis were used to determine the association between redox status biomarkers and cytokines with different patterns of HPA (HPA level, bouts of moderate to vigorous physical activity [MVPA], and multivariate pattern of HPA) in EU and OW/OB preschoolers. RESULTS: OW/OB preschoolers had lower CAT activity, higher levels of TAC, TBARS, and cytokines, and similar levels of HPA to EU preschoolers. In EU preschoolers, SOD activity exhibited a stronger negative association with moderate intensity ranges of HPA (R2 = 0.18), and negative correlation with sTNFRs (r = -0.40 to -0.46). TBARS had a stronger positive association with ranges of light intensity in the multivariate pattern of HPA (R2 = 0.10). In OW/OB preschoolers, the HPA multivariate associative pattern was predominantly from vigorous intensity ranges. Thus, SOD activity had a positive association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (ß [95% CI] = 0.457 [0.0026. 0.0576]). TAC had a negative association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (ß [95% CI] = -0.718 [-0.0025. -0.0003]). Additionally, leptin levels were lower in OW/OB preschoolers engaged in vigorous physical activity (VPA) (8000-9999 counts/min) for longer periods of time. CONCLUSION: The results of this study indicate that OW/OB preschoolers have higher levels of oxidative stress biomarkers and pro-inflammatory cytokines compared to EU preschoolers. Moreover, VPA may exert antioxidative and anti-inflammatory effects in OW/OB preschoolers.


Subject(s)
Leptin , Overweight , Humans , Cross-Sectional Studies , Cytokines , Thiobarbituric Acid Reactive Substances , Body Mass Index , Obesity , Exercise , Oxidation-Reduction , Biomarkers , Multivariate Analysis , Superoxide Dismutase
12.
BMC Musculoskelet Disord ; 24(1): 182, 2023 Mar 11.
Article in English | MEDLINE | ID: mdl-36906535

ABSTRACT

BACKGROUND: The European Working Group on Sarcopenia in Older People 2 (EWGSOP2) proposed the use of different diagnostic tools to assess sarcopenia. This study aimed to determine prevalence rates of sarcopenia according to the diagnostic instruments proposed by EWGSOP2 and to assess their level of agreement in older Brazilian women. METHODS: A cross-sectional study with 161 community-dwelling older Brazilian women. Probable sarcopenia was assessed through Handgrip Strength (HGS) and the 5-times sit-to-stand test (5XSST). In addition to reduced strength, Appendicular Skeletal Muscle Mass (ASM) (obtained by Dual-energy X-ray absorptiometry) and ASM/height² were considered for diagnosis confirmation. Sarcopenia severity was determined by reduced muscle strength and mass and poor functional performance assessed by Gait Speed (GS), Short Physical Performance Battery (SPPB), and Timed Up and Go test (TUG). McNemar's test and Cochran's Q-test were used to compare sarcopenia prevalence. Cohen's Kappa and Fleiss's Kappa tests were used to assess the level of agreement. RESULTS: The prevalence of probable sarcopenia was significantly different (p < 0.05) when using HGS (12.8%) and 5XSST (40.6%). Regarding confirmed sarcopenia, the prevalence was lower when using ASM/height² than with ASM. Regarding severity, the use of SPPB resulted in a higher prevalence in relation to GS and TUG. CONCLUSION: There were differences in the prevalence rates of sarcopenia and low agreement between the diagnostic instruments proposed by the EWGSOP2. The findings suggest that these issues must be considered in the discussion on the concept and assessment of sarcopenia, which could ultimately help to better identify patients with this disease in different populations.


Subject(s)
Sarcopenia , Humans , Female , Aged , Sarcopenia/diagnosis , Hand Strength/physiology , Prevalence , Cross-Sectional Studies , Postural Balance , Time and Motion Studies
13.
BMC Palliat Care ; 22(1): 141, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37749576

ABSTRACT

Paediatric palliative care is needed now more than ever. Medical and technological advances mean that children with complex chronic conditions are surviving longer, necessitating longitudinal support from communities and healthcare systems. Efforts need to be made to ensure our healthcare systems and workforce are equipped to meet the needs of this growing population, including gathering data on the effect of many of our primary and specialty palliative care interventions. BMC Palliative Care has launched a new article Collection on "Paediatric palliative care" to provide an open-access resource for all interested in this topic.


Subject(s)
Hospice and Palliative Care Nursing , Palliative Care , Child , Humans , Quality of Health Care , Technology , Workforce
14.
Clin Gastroenterol Hepatol ; 20(10): 2337-2346.e3, 2022 10.
Article in English | MEDLINE | ID: mdl-34968730

ABSTRACT

BACKGROUND & AIMS: The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn's disease. METHODS: Patients who completed the 52-week study (CELEST) received upadacitinib in the CELEST OLE as follows: those who had received immediate-release upadacitinib 3, 6, or 12 mg twice daily or 24 mg once daily (QD) received extended-release upadacitinib 15 mg QD and those who had received immediate-release upadacitinib 12 or 24 mg twice daily as rescue therapy received extended-release upadacitinib 30 mg QD. If any patient initiating upadacitinib 15 mg QD in CELEST OLE lost response at or after week 4, the dose was escalated to upadacitinib 30 mg QD (dose-escalated group). Clinical, endoscopic, inflammatory and quality-of-life measures were assessed. RESULTS: A total of 107 CELEST study completers entered CELEST OLE. The proportion of patients with clinical remission 2.8/1.0 was maintained between week 0 and month 30 in all groups (month 30: 15 mg, 61%; 30 mg, 54%; dose-escalation, 55%). Endoscopic response was maintained in all groups (month 24: 68%, 67%, and 40%, respectively). The rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, infections, serious infections, herpes zoster, and creatine phosphokinase elevation were higher with upadacitinib 30 mg vs 15 mg. CONCLUSION: Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed in patients with Crohn's disease receiving upadacitinib. Safety over 30 months was consistent with the known safety profile of upadacitinib. CLINICALTRIALS: gov ID no: NCT02782663.


Subject(s)
Crohn Disease , Creatine Kinase/therapeutic use , Crohn Disease/drug therapy , Double-Blind Method , Heterocyclic Compounds, 3-Ring/adverse effects , Humans , Treatment Outcome
15.
BMC Nephrol ; 23(1): 119, 2022 03 24.
Article in English | MEDLINE | ID: mdl-35331148

ABSTRACT

BACKGROUND: Hemodialysis (HD) treatment affects functioning, physical activity level, clinical biomarkers, and body composition. However, the association between these variables with functioning, considering International Classification of Functioning, Disability and Health (ICF) domains remains unclear. Thus, the aim of this study was to investigate the possible association between physical activity, biomarkers, and body composition with functioning in HD patients in reference to the ICF. METHODS: Eighty HD patients performed different tests grouped according to ICF domain: Body structure and function - handgrip strength (HS), 5-repetition sit-to-stand test, and 60-s sit-to-stand test (5-STS, 60-STS, respectively); Activity - short physical performance battery (SPPB); and Participation - participation scale questionnaire. Physical activity [Human Activity Profile questionnaire (HAP)], body composition (Dual-energy X-ray absorptiometry), Parathormone (PTH), and alkaline phosphatase were analyzed as possible variables associated with ICF domains. Data analyses were performed using simple and multiple regression models adjusted for age, duration of HD, and diuresis volume. RESULTS: In the body structure and function domain, appendicular lean mass, PTH level, and age were associated with HS (R2 = 0.558); HAP and PTH were associated with 5-STS (R2 = 0.263); and HAP, PTH, duration of HD, and age were associated with 60-STS (R2 = 0.337). In the activity domain, HAP, PTH, alkaline phosphatase, duration of HD, age, and body fat were associated with SPPB (R2 = 0.689). Finally, only HAP was associated with the participation scale (R2 = 0.067). CONCLUSION: Physical activity and PTH levels are determinant protagonists of functioning in all ICF domains in hemodialysis patients.


Subject(s)
Hand Strength , International Classification of Functioning, Disability and Health , Absorptiometry, Photon , Alkaline Phosphatase , Humans , Parathyroid Hormone , Renal Dialysis
16.
BMC Public Health ; 22(1): 340, 2022 02 17.
Article in English | MEDLINE | ID: mdl-35177034

ABSTRACT

BACKGROUND: Active play opportunities seems to influence the level of physical activity during childhood. However, a gap remains about which environmental opportunities including the daycare physical environment could have a positive impact on the level of physical activity in preschoolers. OBJECTIVES: (1) To develop an index to measure the environmental opportunities of free active play for preschoolers of middle-income countries; (2) to check the relationship and contribution of the index to explain objectively the level of physical activity. METHODS: A quantitative, cross-sectional, exploratory study with 51 preschool children. The established criteria for the index according to the literature were: (1) Outdoor time on typical days of the week. (2) Outdoor time on a typical weekend day. (3) The presence of internal space and external environment in the child's home that allows playing. (4) Presence of patio with space for games at the school. (5) Presence of a playground with a toy at the school. We applied multi-attribute utility theory for the determination of the multicriteria index of physical environmental opportunities. Pearson's correlation analysis and simple linear regression were used to verify the association between the index and the physical activity level. RESULTS: The index showed a positive correlation with the level of physical activity, e.g., the average time of MVPA (r = 0.408, p = 0.003). The univariate linear regression demonstrated that the quality of physical environmental opportunities for physical activity explained 20% of the preschooler's classification as active and 16% of the time in moderate to vigorous physical activity (p < 0.001). CONCLUSION: Physical environmental opportunities for active play have a positive effect on physical activity in preschoolers and should be encouraged in different social segments.


Subject(s)
Accelerometry , Child Day Care Centers , Child , Child, Preschool , Cross-Sectional Studies , Environment , Exercise , Humans
17.
BMC Pediatr ; 22(1): 498, 2022 08 23.
Article in English | MEDLINE | ID: mdl-35999515

ABSTRACT

BACKGROUND: Preschool age (3-5 years old) is a crucial period for children to acquire gross motor skills and develop executive functions (EFs). However, the association between the qualitative gross motor skills and EFs remains unknown in preschoolers, especially among overweight and obese children. METHODS: This was a cross-sectional, exploratory, and quantitative study carried out on 49 preschool children, divided into two subgroups according to their body mass index (overweight/obese: 24; eutrophic [normal weight]: 25). The mean age was 4.59 years. More than half of the sample were boys (55%) and most of the mothers had completed high school (67%) and were class C socioeconomic level (63%). Gross motor skills were assessed using the Test of Gross Motor Development-2, while EFs were evaluated using Semantic verbal fluency (SVF), Tower of Hanoi (TH), Day/Night Stroop, and Delayed Gratification tests. Multiple linear regression models adjusted for sex, age, maternal education, socioeconomic status, quality of the home environment, and quality of the school environment using the stepwise method were executed, considering the cognitive tasks as independent variables and gross motor skills as dependent variable. RESULTS: The overweight/obese preschoolers showed worse locomotor skills than their eutrophic peers and below average gross motor quotient (GMQ). Overweight/obese girls performed worse in OC skills than boys with excess weight. SVF (number of errors) and TH (rule breaks) explained 57.8% of the variance in object control (OC) skills and 40.5% of the variance in GMQ (p < .05) in the overweight/obese children. Surprisingly, there was no significant association between any of the EF tasks and gross motor skills in the eutrophic children. CONCLUSION: A relationship between EF tasks (number of errors in SVF and rule breaks in TH) and gross motor skills (OC and GMQ) was demonstrated in the overweight/obese preschoolers, indicating that worse cognitive flexibility, working memory, planning, and problem solving are associated with worse gross motor skills in this population when compared to eutrophic children.


Subject(s)
Overweight , Pediatric Obesity , Child , Child, Preschool , Cross-Sectional Studies , Executive Function , Female , Humans , Male , Motor Skills
18.
An Acad Bras Cienc ; 94(1): e20200496, 2022.
Article in English | MEDLINE | ID: mdl-35043849

ABSTRACT

Mugil curema is a pelagic fish species and it is considered the most common species of the Mugilidae family on the Brazilian coast. The objective of this study was to compile the existing information on the metazoan parasites of this host, as well as including new records from specimens captured in the Cabedelo city, state of Paraíba, Brazil. In the present study, we listed 81 taxa belonging to ten groups previously recorded for the host M. curema, and included 16 species recorded in the Cabedelo region. Eight out of 16 parasite taxa found in the Cabedelo region are first host records for M. curema: Ligophorus brasiliensis, Ligophorus sp.1, Ligophorus sp.2 (Monogenea), Fellodistomidae gen. sp., Bucephalidae gen. sp. (Digenea), Pharyngodonidae gen. sp. (Nematoda), Piscicolidae gen. sp. (Hirudinea) and Lernaeopodidae gen. sp. (Copepoda). Monogenea was the most abundant taxonomic group, followed by Copepoda. Despite the number of existing parasitological studies on this host species, new records of occurrence were made for the Cabedelo region and for the host, indicating that the knowledge about the parasites associated with this fish species is still under construction, especially because of its wide geographic distribution.


Subject(s)
Parasites , Smegmamorpha , Trematoda , Animals , Brazil , Gills
19.
Geriatr Nurs ; 48: 127-131, 2022.
Article in English | MEDLINE | ID: mdl-36208539

ABSTRACT

Sedentary activities, such as watching television and using the computer, are frequent conditions in older adults and can be associated with sarcopenia. The objectives of this study were: (a) to establish sedentary behavior (SB) cutoff values for screening probable sarcopenia in community-dwelling older adults and (b) to verify the association between SB and probable sarcopenia according to the established cutoff point. This was a cross-sectional study including 1,165 community residents in Florianopolis/SC. SB was assessed using the International Physical Activity Questionnaire. The outcome was probable sarcopenia (assessed by time ≥ 15 s in the Five times sit-to-stand test). The cut-off points found for SB were time > 120 min/day [AUC: 0.54 (95%CI: 0.51; 0.57)] watching TV or video/DVD and ≤ 20 min/day [AUC: 0.59 (95%CI: 0.56;0.62)] using computer/internet. Older adults with SB had 1.30 (95% CI: 1.01; 1.66) and 1.46 (95% CI: 1.08; 1.96) greater chances of having sarcopenia, respectively.


Subject(s)
Sarcopenia , Sedentary Behavior , Humans , Aged , Cross-Sectional Studies , Independent Living
20.
J Vasc Bras ; 21: e20210229, 2022.
Article in English | MEDLINE | ID: mdl-36407663

ABSTRACT

This systematic review aimed to discuss the main findings regarding the reliability and validity of health-related quality of life questionnaires for chronic venous insufficiency. Searches were performed on the MEDLINE, CINAHL, Web of Science, LILACS, and Scopus databases. The search terms used were related to "venous insufficiency", and "quality of life". The CIVIQ-20 and CIVIQ-14 instruments had adequate internal consistency and both were able to discriminate disease severity. The VEINES-QoL showed adequate internal consistency but was not able to discriminate disease severity. Most studies did not demonstrate a correlation between VEINES-QoL and the mental component of the SF-36. The AVVQ had inadequate reliability but its validity was also doubtful when compared to the SF-36. The VARIShort demonstrated good internal consistency, reproducibility, and validity, but only the original study was included. For venous leg ulcers, the CCVUQ showed adequate reliability and validity when compared to VLU-QoL.


Esta revisão sistemática objetivou discutir os principais achados sobre a confiabilidade e validade dos questionários de qualidade de vida relacionada à saúde na insuficiência venosa crônica. A busca foi realizada nas bases de dados MEDLINE, CINAHL, Web of Science, LILACS e Scopus. Os termos de busca foram relacionados a "insuficiência venosa" e "qualidade de vida". O Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ)-20 e o CIVIQ-14 apresentaram consistência interna adequada e foram capazes de discriminar a gravidade da doença. O Venous Insufficiency Epidemiological and Economic Study ­ Quality of Life (VEINES-QoL) apresentou consistência interna adequada, mas não foi capaz de discriminar a gravidade da doença. A maioria dos estudos não demonstrou associação do VEINES-QoL com o componente mental do Short Form Health Survey (SF-36). O Aberdeen Varicose Vein Questionnaire (AVVQ) apresentou confiabilidade inadequada e validade duvidosa quando comparado ao SF-36. O VARIShort demonstrou consistência interna, reprodutibilidade e validade boas, mas apenas o estudo original foi incluído. Na úlcera venosa, o Charing Cross Venous Ulcer Questionnaire (CCVUQ) apresentou confiabilidade e validade adequadas quando comparado ao Venous Leg Ulcer Quality of Life (VLU-QoL).

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