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In this clinical trial, the appetite suppressant sibutramine as compared with placebo resulted in modest weight loss but also in an unexpected increase in the risk of nonfatal myocardial infarction and stroke (a finding limited to patients with preexisting cardiovascular disease). Sibutramine should not be used in patients with cardiovascular disease. Obesity and excess weight are escalating public health concerns because they increase the prevalence of associated conditions such as diabetes mellitus and the risk of premature death. 1 , 2 More than 80% of even highly motivated patients are unable to achieve weight loss with dietary and lifestyle modifications alone. 3 Sibutramine is a norepinephrine and serotonin reuptake inhibitor that was approved for weight management in patients who are unable to lose weight by means of diet and exercise alone. Sibutramine induces satiety (resulting in reduced food intake) and an increase in energy expenditure. 4 , 5 In some patients, sibutramine increases blood pressure, pulse . . .

Background Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. Methods We randomly allocated patients with stage I–III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. Results A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs . 21.2%, P  = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR ( P interaction  = 0.001, P interaction  = 0.012, respectively). There was no significant difference in EFS ( P  = 0.895) or OS ( P  = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A ( P  = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B ( P  = 0.044). Conclusions Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

In this randomized, controlled trial, 224 obese adults were assigned to one of four weight-loss treatments for one year: sibutramine alone, lifestyle modification through group therapy alone, combined therapy, or sibutramine plus brief counseling about lifestyle modification delivered by a physician. Combined therapy resulted in more weight loss than either drug therapy alone or lifestyle modification alone, underscoring the importance of prescribing weight-loss medications in combination with, rather than in lieu of, lifestyle modification. Combined therapy resulted in more weight loss than either drug therapy alone or lifestyle modification alone, underscoring the importance of prescribing weight-loss medications in combination with, rather than in lieu of, lifestyle modification Two medications, sibutramine (Meridia, Abbott Laboratories) and orlistat (Xenical, Roche), are currently approved by the Food and Drug Administration for the induction and maintenance of weight loss. 1 – 5 These agents are recommended as an adjunct to a comprehensive program of diet, exercise, and behavior therapy, 2 , 3 , 6 which is known as lifestyle modification and is delivered in weekly group or individual sessions. 7 – 9 Industry-sponsored trials of weight-loss medications typically have included limited programs of lifestyle modification. 5 , 10 , 11 This randomized trial compared the efficacy of sibutramine alone (as typically prescribed in primary care practice), group sessions of lifestyle modification alone, . . .

Background Peritoneal metastasis (PM) after radical surgery is an important cause of treatment failure in colorectal cancer (CRC). Intraoperative intraperitoneal perfusion chemotherapy may be an effective method for preventing postoperative PM in patients with CRC. This study aimed to explore the safety and feasibility of intraoperatively preventive intraperitoneal perfusion chemotherapy using lobaplatin for CRC. Methods Between 12 December 2017 and 17 October 2019, 720 eligible CRC patients with T4 or N + clinical TNM stage were recruited from 25 hospitals in China. Eligible patients were randomised in a 1:1 ratio to undergo resection of CRC only (control group) or resection of CRC with intraperitoneal perfusion chemotherapy with lobaplatin intraoperatively (lobaplatin group). The primary endpoint of this trial was the rate of PM after surgery, while secondary endpoints included safety, overall survival (OS) time, recurrence-free survival (RFS) time, peritoneal recurrence-free survival (PRFS) time, and the rate of liver metastasis. Results Of 716 patients included in the full analysis set (FAS), 352 were assigned to the lobaplatin group and 364 to the control group. In the FAS population, adding intraoperatively preventive intraperitoneal perfusion chemotherapy with lobaplatin decreased the primary end point rate of 3-year PM (3.56% vs 8.75%, P  = 0.0053). There was no significant difference in the 3-year OS between the groups (93.2% vs 90.4%, P  = 0.1660). The 3-year RFS rate (88.1% vs 81.6%, 0.0146) and 3-year PRFS rate (96.6% vs 91.5%, P  = 0.0053) were significantly higher in the lobaplatin group than the control group. There were no statistically significant differences between the two groups in the incidence (69.77% vs 64.75%) or severity of adverse events (AEs) in the safety set (SS) population. Conclusions Initiation of intraoperatively preventive intraperitoneal perfusion chemotherapy with lobaplatin reduced the 3-year PM rate in CRC patients while improving both 3-year RFS and PRFS. The treatment was well tolerated, and the safety findings were comparable with those of the control group. Trial registration Chinese Clinical Trial Registry, ChiCTR1800014617.

Context: No long-term studies have compared centrally acting drugs for treating obesity. Objective: To compare the efficacy and safety of diethylpropion (DEP), fenproporex (FEN), mazindol (MZD), fluoxetine (FXT) and sibutramine (SIB) in promoting weight loss. Design and Setting: A prospective, randomized, placebo (PCB)-controlled study conducted at a single academic institution. Patients: A total of 174 obese premenopausal women. Intervention: Participants randomly received DEP 75 mg ( n =28), FEN 25 mg ( n =29), MZD 2 mg ( n =29), SIB 15 mg ( n =30), FXT 20 mg ( n =29) or PCB ( n =29) daily over 52 weeks. Diet and physical activity were encouraged. Main Outcome Measures: The primary endpoints were changes in body weight and the proportion of women who achieved at least 5% weight loss by week 52 in the intent-to-treat population. Other measurements included anthropometry, safety, metabolic and cardiovascular parameters. Results: Weight loss was greater than PCB (−3.1±4.3 kg) with DEP (−10.0±6.4 kg; P< 0.001), SIB (−9.5±5.9 kg; P< 0.001), FEN (−7.8±6.9 kg; P< 0.01) and MZD (−7.4±4.9 kg; P< 0.01) but not with FXT (−2.5±4.1 kg). Ten (33.3%) women lost⩾5% of their initial weight with PCB, compared with 20 (71.4%; P< 0.001) with DEP, 20 (69%; P< 0.02) with FEN, 21 (72.4%; P< 0.01) with MZD, 22 (73.3%; P< 0.001) with SIB and 10 (35.5%) with FXT. Each medically treated group experienced more adverse events compared with PCB ( P< 0.001). Compared with PCB, constipation was more prevalent with DEP, SIB and MZD ( P< 0.01); anxiety was more prevalent with DEP ( P= 0.01); and irritability occurred more frequently with DEP and FEN ( P= 0.02). Significant improvements in the depression and anxiety scores, binge-eating episodes and quality of life correlated with weight loss. CONCLUSION: The centrally acting drugs DEP, FEN, MZD and SIB were more effective than PCB in promoting weight loss in obese premenopausal women, with a satisfactory benefit–risk profile.

Background Intragastric balloon (BioEnterics Intragastric Balloon, BIB®) or pharmacotherapy are possible options for the treatment of obese patients when traditional approaches have failed. The aim of our study was to compare in obese patients the effect on weight loss and metabolic changes of lifestyle modifications associated with either BIB or pharmacotherapy or the two treatments in sequence as a maintenance strategy for weight loss. Methods Fifty obese patients were recruited and randomly assigned to lifestyle modifications combined with either BIB for 6 months ( n  = 30) or sibutramine (pharmacotherapy group) for 1 year ( n  = 20). After BIB removal, patients were randomly assigned to either correct lifestyle (BIB/lifestyle) or lifestyle plus pharmacotherapy (BIB/pharmacotherapy). Results At 6 months, patients treated with BIB lost significantly ( P  < 0.05) more weight (percent of initial weight lost, %IWL = 14.5 ± 1.2; percent of excess BMI lost, %EBL = 37.7 ± 3.2) than patients who received pharmacological treatment (%IWL = 9.1 ± 1.5, %EBL = 25.3 ± 4.1). At 1 year, the weight lost was significantly ( P  < 0.05) greater in patients treated with either BIB/pharmacotherapy (%IWL = 15.8 ± 2.3%, %EBL = 41.3 ± 6.7%) or BIB/lifestyle (%IWL = 14.3 ± 2.7, %EBL = 34.9 ± 6.5%) in respect to pharmacotherapy group (%IWL = 8.0 ± 1.4%, %EBL = 22.1 ± 3.9%). Moreover, patients treated sequentially with BIB/lifestyle or BIB/pharmacotherapy showed a significant ( P  < 0.05) improvement in insulin sensitivity and triglycerides levels. Conclusions BIB represents an efficacious long-term obesity treatment when supplemental strategies, as lifestyle modifications or pharmacotherapy, are established for weight maintenance after its removal.

Background This work was to evaluate the perioperative safety and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel in patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. Methods Patients were treated by CRS + HIPEC with lobaplatin 50 mg/m 2 and docetaxel 60 mg/m 2 in 6000 mL of normal saline at 43 ± 0.5 °C for 60 min. Vital signs were recorded for 6 days after CRS + HIPEC procedures. Perioperative serious adverse events (SAE), hematological, hepatic, renal, and electrolytes parameters, the changes in serum tumor markers (TM) before and after operation, patient recovery, and overall survival (OS) were analyzed. Results One hundred consecutive PC patients underwent 105 CRS + HIPEC procedures and postoperative chemotherapy. The median CRS + HIPEC duration was 463 (range, 245–820) min, and the highest temperature and heart rate during six postoperative days were 38.6 °C (median 37.5 °C) and 124 bpm (median 100 bpm), respectively. The 30-day perioperative SAE occurred in 16 (15.2 %) and mortality occurred in 2 (1.9 %) patients. Most routine blood laboratory tests at 1 week after surgery turned normal. Among 82 cases with increased preoperative TM CEA, CA125, and CA199, 71 cases had TM levels reduced or turned normal. Median time to nasogastric tube removal was 5 (range, 3–23) days, to liquid food intake 6 (range, 4–24) days, and to abdominal suture removal 15 (range, 10–30) days. At the median follow-up of 19.7 (range, 7.5–89.2) months, the median OS was 24.2 (95 % CI, 15.0–33.4) months, and the 1-, 3-, and 5-year OS rates were 77.5, 32.5, and 19.8 %, respectively. Univariate analysis identified five independent prognostic factors on OS: the origin of PC, peritoneal cancer index, completeness of CRS, cycles of adjuvant chemotherapy, and SAE. Conclusions CRS + HIPEC with lobaplatin and docetaxel to treat PC is a feasible procedure with acceptable safety and can prolong the survival in selected patients with PC. Trial registration ClinicalTrials.gov, NCT00454519

AIM:: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD:: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT:: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research. INTERNATIONAL JOURNAL OF OBESITY: (2002) 26, 262-273. DOI: 10.1038/sj.ijo.0801889

Background/Objectives: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. Subjects/Methods: A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27–45 kg m –2 were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions. Results: During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (−8.1±10.5 mm Hg with <5 kg weight loss to −10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs. Conclusion: Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.

Objective: Anemia is associated with increased cardiovascular risks. Obesity may cause anemia in several ways, for example, by low-grade inflammation and relative iron deficit. The outcomes associated with anemia in overweight/obese patients at high cardiovascular risk are however not known. Therefore, we investigated the cardiovascular prognosis in overweight/obese subjects with anemia. Methods: A total of 9 687 overweight/obese cardiovascular high-risk patients from the Sibutramine Cardiovascular OUTcomes trial were studied. Patients were stratified after baseline hemoglobin level and followed for the risks of primary event (comprising nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality. Risk estimates (hazard ratios (HR) with 95% confidence intervals (CI)) were calculated using Cox regression models. Results: Anemia was unadjusted associated with increased risk for the primary event, HR 1.73 (CI 1.37–2.18) and HR 2.02 (CI 1.34–3.06) for patients with mild or moderate-to-severe anemia, respectively, compared with patients without anemia. Adjusted for several confounders, anemia remained of prognostic importance. Increased risk of the primary events appeared to be driven by risk of cardiovascular death, adjusted HR 1.82 (CI 1.33–2.51) for mild anemia and adjusted HR 1.65 (CI 0.90–3.04) for moderate-to-severe anemia, and all-cause mortality, adjusted HR 1.50 (CI 1.17–1.93) for mild and adjusted HR 1.61 (CI 1.04–2.51) for moderate-to-severe anemia. While adding serum creatinine to the models, the increased risk of mild anemia was still a significant predictor for mortality (cardiovascular and all-cause), whereas moderate-to-severe anemia was not. For the primary events, anemia was no longer of independent prognostic importance when including serum creatinine. Conclusion: Anemia is associated with an increased risk of long-term adverse cardiovascular events and deaths among overweight/obese cardiovascular high-risk patients. The increased risk appeared to be driven by the risk of cardiovascular death and all-cause mortality, and renal impairments seemed to have a role in the increased risk.