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BACKGROUND: There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy. METHODS: FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16-80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal [subcutaneous placebo]). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index [CDAI] in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102. FINDINGS: 712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% [95% CI 5-24]; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% [5-25]; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% [19-37]). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission [p=0·124]) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 [55%] of 157 patients, adjusted difference 15% [95% CI 5-24]; endoscopic response 74 [47%] of 157, adjusted difference 26% [17-35]). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose-response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache. INTERPRETATION: Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease. FUNDING: AbbVie.
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Enfermedad de Crohn , Dolor Abdominal , Anticuerpos Monoclonales/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Método Doble Ciego , HumanosRESUMEN
BACKGROUND: Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. METHODS: ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. FINDINGS: Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. INTERPRETATION: Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. FUNDING: AbbVie.
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Productos Biológicos , Enfermedad de Crohn , Dolor Abdominal , Anticuerpos Monoclonales , Productos Biológicos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Humanos , Quimioterapia de InducciónRESUMEN
BACKGROUND: Individuals with inflammatory bowel disease (IBD) experience cycles of aggressive physical symptoms including abdominal pain, diarrhea, and fatigue. These acute symptoms regress and return, and chronic symptoms and complications often linger. The nature of the disease can also cause individuals to experience psychological distress including symptoms of anxiety and depression; however, unlike the physical symptoms of IBD, these psychological symptoms often remain untreated. OBJECTIVE: This study aims to evaluate the feasibility, acceptability, and effectiveness of virtual mindfulness-based stress reduction (v-MBSR) for adults with IBD. METHODS: IBD patients with self-reported anxiety or depression were recruited from clinics in Alberta, Canada to participate in an 8-week v-MSBR intervention. Eligible patients participated in v-MBSR delivered by psychiatrists using a videoconferencing platform. Primary feasibility outcomes included trial uptake, adherence, attendance, and attrition rates. Secondary effectiveness outcomes included measures of anxiety, depression, quality of life (QoL), and mindfulness. Effectiveness data were collected at 3 time points: baseline, at intervention completion, and 6 months after completion. To further assess feasibility and acceptability, participants were invited to participate in a semistructured interview after completing v-MBSR. RESULTS: A total of 16 of the 64 (25%) referred patients agreed to participate in v-MBSR with the most common reason for decline being a lack of time while 7 of the 16 (43.8%) participants completed the program and experienced encouraging effects including decreased anxiety and depression symptoms and increased health-related QoL with both improvements persisting at 6-month follow-up. Participants described improved coping strategies and disease management techniques as benefits of v-MBSR. CONCLUSIONS: Patients with IBD were interested in a psychiatrist-led virtual anxiety management intervention, but results demonstrate v-MBSR may be too time intensive for some patients with IBD patients. v-MBSR was acceptable to those who completed the intervention, and improvements to anxiety, depression, and QoL were promising and sustainable. Future studies should attempt to characterize the patients with IBD who may benefit most from interventions like v-MBSR.
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Background: Online stress reduction interventions may be useful adjuncts to standard medical therapies for inflammatory bowel disease (IBD). As part of the evaluation of a 12-week randomized control trial (RCT) of an online multicomponent stress reduction program, our aim for the current study was to use qualitative methods to more deeply explore the patient experience with the online programming. Methods: Upon completion of the 12-week RCT, all intervention participants were invited to participate in semistructured interviews. A qualitative descriptive approach was used. Interviews were analyzed through a theoretical thematic analysis process, whereby transcripts were coded, and codes then grouped into larger categories and themes. Results: A total of 56 interviews were analyzed with the emergence of 3 main themes: (1) IBD as a source of stress and uncertainty, (2) understanding the positive impacts of the stress reduction program, and (3) suggested strategies to enhance program desirability. IBD was described as causing uncertainty, significant disruptions to daily activities, and stress, which in turn worsened symptoms. The online program was associated with a perceived reduction in IBD symptom burden, an increased ability to manage daily and disease-associated stressors, and a more positive mindset. Variation in program content and fostering connections with others in the IBD community were identified as potential strategies to enhance future programming. Conclusions: This qualitative companion study highlights the power of the patient voice to deepen our understanding of the impact of IBD, and the potential benefit of an online stress reduction program including suggestions for iterative refinement.
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Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design. Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD. Design: This is a RCT. Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2-3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen's Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences. Results: Of 150 screened patients, 101 were randomized to the intervention (n = 49) and control (n = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn's disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5-34.3, p < 0.001). Significant improvements were seen in mental health, resilience, and HRQoL measures, with a median satisfaction score of 89/100 at the end of the 12 weeks. In the 44/49 patients who completed the intervention, 91% achieved program adherence targets. Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course. Registration: ClinicalTrials.gov Identifier NCT03831750. Plain Language Summary: An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2-3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention.
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BACKGROUND & AIMS: Dyspepsia and irritable bowel syndrome (IBS) are common conditions that can coexist in patients. We performed a systematic review and meta-analysis to estimate prevalence of IBS in dyspepsia. METHODS: Relevant articles published through August 2008 were identified from MEDLINE and EMBASE literature searches (23,457 citations). Eligible studies included adults recruited from the community, the workplace, blood donation or screening clinics, and family physician offices or internal medicine clinics. Selected studies reported prevalence of dyspepsia and IBS within the same population. The prevalence of IBS in subjects with and without dyspepsia was pooled for all studies and compared. Odds ratios (OR) and confidence intervals (CI) were calculated. The degree of overlap between dyspepsia and IBS was determined. RESULTS: Of 239 papers evaluated, 150 reported prevalence of dyspepsia and 19 (involving 18,173 subjects) reported the proportion of subjects with IBS within the same population. The prevalence of dyspepsia was 27% (95% CI, 23%-31%). The prevalence of IBS in subjects with dyspepsia was 37% (95% CI, 30%-45%) compared with 7% (95% CI, 5%-10%) in those without. The pooled OR for IBS in subjects with dyspepsia was 8 (95% CI, 5.74-11.16). The degree of overlap between the 2 conditions varied from 15% to 42%, depending on diagnostic criteria used for each. CONCLUSIONS: Individuals with dyspepsia have an 8-fold increase in prevalence of IBS compared with the population. The strength of the association suggests common pathogenic mechanisms. Dyspeptic patients should be assessed routinely for IBS.
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Dispepsia/complicaciones , Dispepsia/epidemiología , Síndrome del Colon Irritable/complicaciones , Síndrome del Colon Irritable/epidemiología , Comorbilidad , Humanos , PrevalenciaRESUMEN
BACKGROUND & AIMS: Evolving definitions of dyspepsia may lead to differences in the prevalence of clinically significant findings encountered at upper gastrointestinal (GI) endoscopy in sufferers. However, few studies report the prevalence of endoscopic findings in individuals with dyspepsia. We conducted a systematic review and meta-analysis examining this. METHODS: MEDLINE and EMBASE were searched through April 2010 to identify relevant articles (23,457 citations). Eligible studies recruited adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform upper gastrointestinal endoscopy in a proportion of, or all, participants. Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies, and compared using odds ratios and 95% confidence intervals. RESULTS: Of 240 papers evaluated, 151 reported prevalence of dyspepsia. Nine reported prevalence of endoscopic findings among 5389 participants. Erosive esophagitis was the most common abnormality encountered (pooled prevalence 13.4%) followed by peptic ulcer (pooled prevalence 8.0%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 2.07; 95% confidence interval, 1.52-2.82). Prevalence of erosive esophagitis was lower when the Rome criteria were used to define dyspepsia compared with a broad definition (6% vs 20%). CONCLUSIONS: Erosive esophagitis was the most common finding encountered at endoscopy for dyspepsia, though prevalence was lower when the Rome criteria were used to define dyspepsia. Only peptic ulcer was more common in individuals with dyspepsia.
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Dispepsia/epidemiología , Dispepsia/etiología , Endoscopía Gastrointestinal , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/diagnóstico , Adulto , Humanos , PrevalenciaRESUMEN
Drag area (Ad ) is a primary factor determining aerodynamic resistance during level cycling and is therefore a key determinant of level time trial performance. However, Ad has traditionally been difficult to measure. Our purpose was to determine the value of adding field-measured Ad as a correlate of level cycling time trial performance. In the field, 19 male cyclists performed a level (22.1 km) time trial. Separately, field-determined Ad and rolling resistance were calculated for subjects along with projected frontal area assessed directly (AP ) and indirectly (Est AP ). Also, a graded exercise test was performed to determine [Formula: see text] peak, lactate threshold (LT), and economy. [Formula: see text] peak ([Formula: see text]) and power at LT were significantly correlated to power measured during the time trial (r = 0.83 and 0.69, respectively) but were not significantly correlated to performance time (r = - 0.42 and -0.45). The correlation with performance time improved significantly (p < 0.05) when these variables were normalized to Ad . Of note, Ad alone was better correlated to performance time (r = 0.85, p < 0.001) than any combination of non-normalized physiological measure. The best correlate with performance time was field-measured power output during the time trial normalized to Ad (r = - 0.92). AP only accounted for 54% of the variability in Ad . Accordingly, the correlation to performance time was significantly lower using power normalized to AP (r = - 0.75) or Est AP (r = - 0.71). In conclusion, unless normalized to Ad , level time trial performance in the field was not highly correlated to common laboratory measures. Furthermore, our field-measured Ad is easy to determine and was the single best predictor of level time trial performance.
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AIM: To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy. METHODS: Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n=382); (2) medically refractory requiring emergent colectomy (n=309); and (3) elective colectomy (n=329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI. RESULTS: The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR=3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR=5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR=1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. CONCLUSION: VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.
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Colectomía/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/cirugía , Fármacos Gastrointestinales/uso terapéutico , Tromboembolia Venosa/etiología , Adolescente , Adulto , Anticoagulantes/uso terapéutico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Procedimientos Quirúrgicos Electivos , Urgencias Médicas , Femenino , Fármacos Gastrointestinales/efectos adversos , Heparina/uso terapéutico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/prevención & control , Adulto JovenRESUMEN
PURPOSE: Pre-clinical and early-phase clinical studies have demonstrated that dexamethasone (DEX) administration prior to chemotherapy reduces toxicity and enhances efficacy in the treatment of cancer. We undertook a randomized, phase II multi-institutional trial to evaluate these effects in patients with Stage IV non-small cell lung cancer. METHODS: Patients were treated with carboplatin on day 1 and gemcitabine on days 1 and 8 every 21 days, for up to 6 cycles. Patients were randomized not to receive (Arm 1, n = 25) or to receive (Arm 2, n = 31) DEX orally for 4 days prior to chemotherapy on days 1 and 8. The primary endpoint was the incidence/course of grade 3 and 4 hematologic toxicity. Secondary endpoints included efficacy [response and overall survival (OS)] and evaluation of the Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, to predict survival and toxicity. RESULTS: The incidence/course of grade 3 and 4 hematologic toxicity was significantly reduced in Arm 2 (DEX) versus Arm 1 (no DEX): neutrophils = 13 versus 40 % (p = 0.009) and platelets = 23 versus 44 % (p = 0.03). Response rates and OS were higher in Arm 2 versus Arm 1: 8/31 versus 2/25 (partial response, p = ns) and 378 versus 291 days (p = ns). The GPS significantly predicted survival OS (p = 0.04) but not toxicity. CONCLUSIONS: Pre-treating patients with DEX is a safe, effective, and economic method of reducing the hematologic toxicity of carboplatin and gemcitabine. Our data suggest efficacy may also be enhanced by DEX pre-treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Proteína C-Reactiva/metabolismo , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Dexametasona/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Albúmina Sérica/metabolismo , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
Crohn's disease and ulcerative colitis are chronic inflammatory gastrointestinal disorders which often result in significant morbidity or surgery. Current treatment options are not curative and may cause significant adverse effects. The introduction of anti-tumour necrosis factor alpha (anti-TNFα) therapy over a decade ago was a welcome addition to the therapeutic armamentarium and revolutionized the treatment of inflammatory bowel disease (IBD). Despite their relative success, a significant proportion of patients with IBD fail to respond or subsequently lose response anti-TNFα therapy. This review identifies and explores the role of drug levels and immunogenicity (antibody formation) on the efficacy of anti-TNFα therapy and details how monitoring these parameters may help to optimize the management of patients with IBD.
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PURPOSE: To compare the demands of a 6-d stage race using field measures of power output and HR in male (n=8) and female (n=10) competitive cyclists. METHODS: HR and power output were monitored in males and females competing in separate races on identical courses including a prolog (4 km), four circuit/road races (mean ± SD: 118 ± 23 km), and a criterium (47 km). All subjects participated in laboratory-based exercise testing within 2 wk of the race. RESULTS: Compared with females, males took 10%, 22%, and 10% less time to complete the prolog, circuit/road races, and criterium, respectively. For males, power output in the prolog, circuit/road races, and criterium averaged 405, 247, and 278 W, respectively. For females, power output averaged 295, 160, and 205 W, respectively. During the prolog, the percent time spent below, at, and above the lactate threshold was 29%, 9%, and 62%, respectively, for males and 24%, 7%, and 69%, respectively, for females. For the circuit/road races, these values were 57%, 10%, and 33%, respectively, for males and 62%, 10%, and 28%, respectively, for females. During the criterium, these values were 51%, 6%, and 43%, respectively, for males, and 50%, 8%, and 42%, respectively, for females. CONCLUSIONS: Although men had faster finishing times and higher absolute power outputs, no significant difference was found between men and women in their relative power response. These findings suggest that pacing strategy is based on relative exercise responses and not on absolute exercise responses.
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Rendimiento Atlético/fisiología , Ciclismo/fisiología , Adulto , Femenino , Humanos , Masculino , Fuerza Muscular/fisiología , Consumo de Oxígeno/fisiología , Pennsylvania , Factores Sexuales , Deportes , Telemetría , Adulto JovenRESUMEN
PURPOSE: To develop a protocol for isolating changes in aerodynamic and rolling resistances from field-based measures of power and velocity during level bicycling. METHODS: We assessed the effect of body position (hands on brake hoods vs drops) and tire pressure changes (414 vs 828 kPa) on aerodynamic and rolling resistances by measuring the power (Pext)-versus-speed (V) relationship using commercially available bicycle-mounted power meters. Measurements were obtained using standard road bicycles in calm wind (<1.0 m·s) conditions at constant velocities (acceleration <0.5 m·s) on a flat 200-m section of a smooth asphalt road. For each experimental condition, experienced road cyclists rode in 50-W increments from 100 to 300 W for women (n=2) or 100 to 400 W for men (n=6). Aerodynamic resistance per velocity squared (k) was calculated as the slope of a linear plot of tractive resistance (RT=power/velocity) versus velocity squared. Rolling resistance (Rr) was calculated as the intercept of this relationship. RESULTS: Aerodynamic resistance per velocity squared (k) was significantly greater (P<0.05) while riding on the brake hoods compared with the drops (mean ± SD: 0.175 ± 0.025 vs 0.155 ± 0.03 N·V). Rolling resistance was significantly greater at 60 psi compared with 120 psi (5.575 ± 0.695 vs 4.215 ± 0.815 N). CONCLUSIONS: These results demonstrate that commercially available power meters are sensitive enough to independently detect the changes in aerodynamic and rolling resistances associated with modest changes in body position and substantial changes in tire pressure.