Summary Background Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic ...castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer. Methods TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic, community, and private health-care provision sites across North America and Europe. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive enzalutamide 160 mg/day or bicalutamide 50 mg/day, both taken orally, in addition to ADT, until disease progression. Patients were stratified by a permutated block method (block size of four), by whether bilateral orchiectomy or receipt of luteinising hormone-releasing hormone agonist or antagonist therapy started before or after the diagnosis of metastases, and by study site. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary endpoint was progression-free survival, analysed in all randomised patients. Safety outcomes were analysed in all patients who received at least one dose of study drug. The open-label period of the trial is in progress, wherein patients still on treatment at the end of the double-blind treatment period were offered open-label enzalutamide at the discretion of the patient and study investigator. This trial is registered with ClinicalTrials.gov , number NCT01288911. Findings Between March 22, 2011, and July 11, 2013, 375 patients were randomly assigned, 184 to enzalutamide and 191 to bicalutamide. 126 (68%) and 168 (88%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 20·0 months (IQR 15·0–25·6) in the enzalutamide group and 16·7 months (10·2–21·9) in the bicalutamide group. Patients in the enzalutamide group had significantly improved median progression-free survival (15·7 months 95% CI 11·5–19·4) compared with patients in the bicalutamide group (5·8 months 4·8–8·1; hazard ratio 0·44 95% CI 0·34–0·57; p<0·0001). Of the most common adverse events, those occurring more frequently with enzalutamide than with bicalutamide were fatigue (51 28% of 183 patients in the enzalutamide group vs 38 20% of 189 in the bicalutamide group), back pain (35 19% vs 34 18%), and hot flush (27 15% vs 21 11%); those occurring more frequently with bicalutamide were nausea (26 14% vs 33 17%), constipation (23 13% vs 25 13%), and arthralgia (18 10% vs 30 16%). The most common grade 3 or worse adverse events in the enzalutamide or bicalutamide treatment groups, respectively, were hypertension (13 7% vs eight 4%), hydronephrosis (three 2% vs seven 4%), back pain (five 3% vs three 2%), pathological fracture (five 3% vs two 1%), dyspnoea (four 2% vs one 1%), bone pain (one 1% vs four 2%), congestive cardiac failure (four 2% vs two 1%), myocardial infarction (five 3% vs none), and anaemia (four 2% vs none). Serious adverse events were reported by 57 (31%) of 183 patients and 44 (23%) of 189 patients in the enzalutamide and bicalutamide groups, respectively. One of the nine deaths in the enzalutamide group was thought to be possibly related to treatment (due to systemic inflammatory response syndrome) compared with none of the three deaths in the bicalutamide group. Interpretation The data from the TERRAIN trial support the use of enzalutamide rather than bicalutamide in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Funding Astellas Pharma, Inc and Medivation, Inc.
Objectives This study sought to report the effect of carotid artery stenting (CS) on neurocognitive function (NCF) in patients with severe carotid artery occlusive disease, depending on baseline ...brain perfusion status. Background The effect of CS on NCF has been controversial. Methods We prospectively enrolled 61 patients with carotid artery disease (22 with occlusion, 39 with severe stenosis) in whom CS was attempted. Computed tomography perfusion and NCF assessments including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive subscale (ADAS-Cog), verbal fluency, and Color Trails Test Parts 1 and 2 were applied before and 3 months after intervention. Results Successful recanalization was achieved in 14 of 22 occlusion patients (64%) and in all 39 severe stenosis patients. Two cases were excluded due to procedural cerebral complications. The patients were divided into 3 groups: group 1 (n = 8) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS failed; group 2 (n = 33) consisted of patients with abnormal baseline ipsilateral cerebral perfusion in whom CS was successful; and group 3 (n = 19) consisted of patients without abnormal baseline ipsilateral cerebral perfusion in whom CS was successful. The demographics and baseline NCF were similar among groups. Only in group 2 was there significant improvement in ADAS-Cog (pre-procedure median interquartile range: 6 4 to 9 vs. post-procedure: 5 3 to 7, p = 0.002), MMSE (pre-procedure: 27 25 to 28 vs. post-procedure: 28 25 to 29, p = 0.004) and Color Trails Test Part 1 (pre-procedure: 100 78.5 to 136.5 s vs. post-procedure: 97 60 to 128.5 s, p = 0.003) after CS. Significant difference in changes from baseline was observed only in the Color Trails Test Part 1 among groups (group 1 vs. 2 vs. 3: 1.5 −14 to 11.5 vs. −12.5 −36.5 to 0.5 vs. −0.5 −11 to 27, p = 0.0159). Significant correlation between the change of ipsilateral brain perfusion and MMSE (r = −0.33, p = 0.01) was also identified. Conclusions Successful CS for severe carotid stenosis/occlusion improves NCF, but only in patients with objective baseline abnormal cerebral perfusion.
Abstract Background: When patients return to the emergency department (ED) shortly after being seen, it is generally assumed that their initial evaluation or treatment was inadequate. Objectives: The ...purpose of this study was to determine the rates and causes of revisits to the ED of a 710-bed secondary teaching referral hospital (Kuang Tien General Hospital), to identify areas for improvement, and to define the initial ED presentations that are associated with such revisits. Methods: The study period was from January 1, 2006 to December 31, 2006. There were 34,714 patients seen and discharged in the ED; 1899 patients returned within 72 h. Monthly revisit rates were calculated. The patients who revisited the ED within 72 h were retrospectively identified by the authors, and their charts were examined to determine the causes of the revisits. Results: There were 1899 patients (5.47% of total) found to have revisited the ED within 72 h after their initial visit. The monthly revisit rates ranged from 2.85% to 6.25% (average, 5.47%). The rates of revisits that were related to factors of illness, patients, and doctors were 80.9%, 10.9%, and 8.2%, respectively. Among the factors related to doctors, 3.7% (70 cases) were misdiagnosis, and abdominal pain was the most common presentation (55.7%, 39/70). The most common initial ED presentations were for abdominal pain (12.9%), fever (12.6%), vertigo (4.5%), headache (2.1), and upper respiratory infection (2.1%). Conclusions: Unplanned ED revisits are associated with medical errors in prognosis, treatment, follow-up care, and information. Differentiation between the natural course of a disease, suboptimal therapy, over-anxious reaction of the patient, and medical errors is difficult. Although this study indicates that most revisits are illness-related, further prospective studies are needed to evaluate the most common and the most serious causes of revisits to see if improvements can be made.
Abstract Background Rescuers that undergo acute ascent without acclimatization can experience acute mountain sickness. Although performing cardiopulmonary resuscitation (CPR) for a short period ...requires intensive effort at sea level, performing CPR at high altitude is even more exhausting and can endanger the rescuer. Therefore, we conducted a pilot study to compare the quality of resuscitation in health professionals at high altitude (3100 m) and that at sea level. Methods Thirty-eight participants were asked to performed continuous chest compression CPR (CCC-CPR) for 5 minutes at sea level and at high altitude. Cardiopulmonary resuscitation recording technology was used to objectively quantify the quality of the chest compressions (CCs), including the depth and rate thereof. Results At high altitude, rescuers showed a statistically significant decrease in blood oxygen saturation and an increase in systolic blood pressure, diastolic blood pressure, heart rate, and fatigue, as measured with the Borg score, after CCC-CPR compared with resting levels. The analysis of the time-dependent deterioration in the quality of CCC-CPR showed that the depth of CCs declined from the mean depth of the first 30 seconds after CCC-CPR to that at more than 120 seconds after CCC-CPR at both sea level and high altitude. The average number of effective CCs declined after CCC-CPR was performed for 1 minute at sea level and high altitude. Conclusions The quality of CC rapidly declined at high altitude. At high altitude, the average number of effective CC decreases; and this decrease became significant after continuous CCs had been performed for 1 minute.
Abstract Bone prosthesis composite (BPC) had been widely-used in reconstruction after wide excision of malignant tumors around the knee. However, implant selection for BPC remains a dilemma. ...Forty-one patients with high-grade malignant bone tumors around the knee who underwent excision and reconstruction with BPC and rotating hinged knee (RHK) prosthesis were included. The mean follow-up time was 54 months (range, 31–78 months). The average Musculoskeletal Tumor Society Rating score was 93.4% (range, 73–100%). The mean range of motion was 125°. Complications included 2 local recurrences, 2 nonunions, and 1 peri-prosthetic fracture. The reconstruction with BPC using the RHK prosthesis provided consistently good functional results with a low complication rate. The RHK prosthesis is a promising choice for BPC reconstruction.
Because of unsatisfactory sugar control, she started empagliflozin at 25 mg/d a few days before ED presentation. Once the patient complained having nausea, vomiting, abdominal pain, or general ...lethargy, who had received SGLT2 inhibitors, the patient should be evaluated for the presence of metabolic acidosis and ketosis despite having a normal blood glucose level.
Abstract Chang Y-C, Chen S-Y, Ting L-L, Peng SS, Wang T-C, Wang T-G. A 2-year follow-up of swallowing function after radiation therapy in patients with nasopharyngeal carcinoma. Objective To evaluate ...over a 2-year period the serial swallowing function of patients with nasopharyngeal carcinoma (NPC) after completing radiotherapy (RT). Design Prospective longitudinal follow-up. Setting University hospital. Participants Patients with NPC (N=76) referred for RT: 53 of them at 1 year after RT, and 23 at 2 years after RT. Interventions Not applicable. Main Outcome Measures Participants completed a questionnaire and had a video-recorded fluoroscopic swallowing study before RT and 1 month, 1 year, and 2 years after RT. Results The highest incidence of dysphagia symptoms and retropharyngeal soft tissue swelling occurred in the first month after RT and decreased over time. Pharyngeal transit time was prolonged continuously up to 1 year after RT. Epiglottic vallecular stasis and pharyngeal mucosal coating were worst in the first month after RT and stable afterwards. Aspiration was uncommon during the first 2 years after RT. Conclusions At a 2-year follow-up after RT, patients with NPC had a progressively increasing pharyngeal transit time, although the subjectively identified symptoms of dysphagia decreased after the first month after RT.
ED presentations of acute renal infarction Huang, Chien-Cheng, MD; Lo, Hong-Chang, MD; Huang, Hsien-Hao, MD ...
The American journal of emergency medicine,
02/2007, Letnik:
25, Številka:
2
Journal Article
Recenzirano
Abstract Objective The objective of the study was to investigate initial clinical characteristics that can suggest an early diagnosis of patients with acute renal infarction presenting with flank ...and/or abdominal pain in the emergency department (ED). Methods From January 1, 1996, through December 31, 2005, 20 adult patients with renal infarction diagnosed by contrast-enhanced computed tomography in the ED were enrolled. Medical records, including demographic data, risk factors for thromboembolism, initial clinical presentations, laboratory data, treatment programs and outcomes, were retrospectively reviewed and analyzed. Results Mean patient age was 60.3 years (range, 21-80). The estimated incidence of renal infarction was 0.004% (20 of 481 540) among the ED census. The median time of onset of symptoms before the ED visit was 31 hours (range, 1-285). Eighteen patients (90%) had a history of more than 1 risk factor for thromboembolic events. In clinical presentations, all the patients had either abdominal or flank pain and tenderness. Nineteen patients (95%) had an elevated serum lactate dehydrogenase level with a mean ± SD of 812.1 ± 569.4 U/L. Sixteen patients (80%) presented with the triad—persisting flank or abdominal pain/tenderness, elevated serum lactate dehydrogenase level, and proteinuria. Among all 20 patients, 10 patients (50%) were diagnosed as having renal infarction at the initial ED visit. No specific clinical characteristics could be identified to distinguish those patients diagnosed early and those with delayed diagnosis. All 20 patients received medical treatment with coumadin, which was given in combination with heparin treatment in 11, peripheral intravenous and/or local intra-arterial thrombolytics with urokinase in 5, and mitral valve replacement in 1. No patient died. Although 4 patients had a mildly elevated serum creatinine level (>1.5 mg/dL) during hospitalization, none of them needs dialysis after more than 1 year of follow-up. Conclusions In this study, we delineated specifically clinical features for emergency physicians to raise their suspicion index for an early diagnosis of patients with renal infarction, a disease which is uncommon and is usually delayed or missed at initial ED presentation.
Summary Background Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic ...castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this phase 3, double-blind, placebo-controlled trial, we recruited patients with progressive metastatic castration-resistant prostate cancer and no previous chemotherapy from 324 study centres (ie, hospitals or large urologic or group outpatient offices) in 43 countries. Eligible patients were randomly assigned in a 1:1 ratio to receive either 400 mg orteronel plus 5 mg prednisone twice daily or placebo plus 5 mg prednisone twice daily. Randomisation was done centrally with an interactive voice response system and patients were stratified by region (Europe, North America, and not Europe or North America) and the presence or absence of radiographic disease progression at baseline. The two primary endpoints were radiographic progression-free survival and overall survival, determined in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT01193244. Findings From Oct 31, 2010, to June 29, 2012, 2353 patients were assessed for eligibility. Of those, 1560 were randomly assigned to receive either orteronel plus prednisone (n=781) or placebo plus prednisone (n=779). The clinical cutoff date for the final analysis was Jan 15, 2014 (with 611 deaths). Median follow-up for radiographic progression-free survival was 8·4 months (IQR 3·7–16·6). Median radiographic progression-free survival was 13·8 months (95% CI 13·1–14·9) with orteronel plus prednisone and 8·7 months (8·3–10·9) with placebo plus prednisone (hazard ratio HR 0·71, 95% CI 0·63–0·80; p<0·0001). After a median follow-up of 20·7 months (IQR 14·2–25·4), median overall survival was 31·4 months (95% CI 28·6–not estimable) with orteronel plus prednisone and 29·5 months (27·0–not estimable) with placebo plus prednisone (HR 0·92, 95% CI 0·79–1·08; p=0·31). The most common grade 3 or worse adverse events were increased lipase (137 17% of 784 patients in the orteronel plus prednisone group vs 14 2% of 770 patients in the placebo plus prednisone group), increased amylase (77 10% vs nine 1%), fatigue (50 6% vs 14 2%), and pulmonary embolism (40 5% vs 27 4%). Serious adverse events were reported in 358 46% patients receiving orteronel plus prednisone and in 292 38% patients receiving placebo plus prednisone. Interpretation In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone. However, no improvement was noted in the other primary endpoint, overall survival. Orteronel plus prednisone was associated with increased toxic effects compared with placebo plus prednisone. On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer. Funding Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Abstract Objective The objective of this study is to determine the association between the duration of high-altitude (> 3000 m) pre-exposure and acute mountain sickness (AMS) incidence. Methods A ...prospective observational study was conducted on 2 random days each month from April 2007 to March 2008 at Paiyun Lodge (3402 m), Jade Mountain, Taiwan. Demographic data, prior AMS history, symptoms, and scores and the days and times of high-altitude pre-exposure within the preceding 2 months were obtained from lowland (< 1500 m) trekkers. Results Totally, 1010 questionnaires were analyzed; 106, 76, and 828 trekkers had pre-exposure lasting at least 3 days (group 1), less than 3 days (group 2), and 0 days (group 3), respectively. Acute mountain sickness incidence was significantly higher in groups 2 and 3 than in group 1 (21.70%, 35.53%, 37.08%, respectively; P = .008). Logistic regression analysis indicated a significantly lower AMS risk in group 1 (group 1, P = .004; odds ratio OR, 0.479; 95% confidence interval CI, 0.290-0.791; group 2, P = .226; OR, 0.725; 95% CI, 0.430-1.221). In group 1, 28 and 78 trekkers had single and intermittent multiple pre-exposure, respectively. There was no difference in the incidence or severity of AMS symptoms between single and intermittent multiple pre-exposure (AMS, P = .838; headache, P = .891; dizziness or lightheadedness, P = .414; fatigue and/or weakness, P = .957; gastrointestinal symptoms, P = .257; difficulty sleeping, P = .804; AMS score, P = .796). Conclusions High-altitude pre-exposure lasting at least 3 days within the preceding 2 months was associated with a significant lower AMS incidence during a subsequent ascent among Jade Mountain trekkers.