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At least 433 records · Page 24Linked to original sources

Placebo controls in randomized trials of acupuncture.

Considerable intellectual and practical effort has been expended on designing and evaluating placebo controls in acupuncture studies. Somewhat less attention has been paid to the question: Why use a placebo in a randomized trial of acupuncture? This is partly because placebo controls have generally been seen as an inherent part of randomized trial methodology. As a result, most acupuncture trials have included a placebo-control group. A large number of different placebo techniques have been used in these trials. The design and choice of placebo techniques has typically depended on purely theoretical considerations, without empirical validation of physiological inactivity and psychological credibility. Principles can be developed for deciding whether to use placebo or another form of control in a randomized trial. These include issues of ethics, practicality and methodology. Such principles apply regardless of the intervention; they can and should be applied to acupuncture research.

Acupuncture Therapy↗

Prospective randomized trials affect the outcomes of intraabdominal infection.

OBJECTIVE: To compare the characteristics and outcomes of patients with intraabdominal infections enrolled in prospective randomized trials (PRTs) with those of a cohort of patients not enrolled in a trial. SUMMARY BACKGROUND DATA: Prospective randomized trials are the gold standard for the evaluation of new treatments. Patients are screened using rigorous eligibility criteria and sometimes are excluded from PRTs because of associated medical conditions or more severe illness. However, the effect that the exclusion of these patients has on the applicability of clinical trial outcomes has not been defined. METHODS: One hundred sixty-eight adults with intraabdominal infection were treated at a single institution during 7 years. Fifty-three patients were enrolled in four PRTs comparing various antibiotic regimens for treatment; 115 were not enrolled. Patient characteristics and outcomes of these two groups were compared. RESULTS: Patients with infections from appendicitis (n = 68) had a low severity of illness and similar outcomes in both groups. These patients and those for whom a concurrent PRT was unavailable were excluded from subsequent analysis. Eighty-eight patients (42 PRT, 46 not enrolled) with serious infection remained for analysis. Patients enrolled in PRTs were younger, had less severe illness, had a decreased length of stay, a lower incidence of antibiotic resistance, and less frequent extraabdominal infections than those not enrolled in a trial. Patients enrolled in PRTs were more likely to be cured and were less likely to die. Logistic regression analysis demonstrated that cure was associated with a lower initial severity of illness, absence of antibiotic resistance, and participation in a PRT. CONCLUSIONS: Patients with intraabdominal infection enrolled in PRTs have an increased likelihood of cure and survival. This is due in part to a lower incidence of antibiotic resistance, which may reflect improved drug selection. Patients not enrolled in PRTs are at greater risk for treatment failure and death because of concomitant illness. Outcomes from PRTs may not be applicable to all patients with intraabdominal infections.

Abdomen↗

Lessons learned from enrollment in the BEST study--a multicenter, randomized trial of group psychosocial support in metastatic breast cancer.

The BEST study, a multicenter randomized trial of group psychosocial support in metastatic breast cancer, had several unusual features that may have influenced recruitment, notably the group nature of the intervention and the need for close collaboration between medical and psychosocial investigators. The recruitment process was examined in light of these features. Establishment of study centers was facilitated by involvement of experienced medical investigators who had successfully collaborated in previous research projects. Systematic evaluation of potential subjects or direct recruitment by psychosocial investigators optimized recruitment; however, the group nature of the intervention prolonged recruitment. Overall, 652 women were approached and 237 (43.3% of those medically eligible) randomized. Using population-based estimates, 24.3% of women with metastatic breast cancer were assessed for the study and 8.7% randomized. A randomization ratio of 2:1 was required to form and maintain groups. Competing clinical trials were the greatest barrier to recruitment. Five lessons were learned during recruitment for this trial: (1) multicenter randomized trials of psychosocial interventions are feasible, even in very ill patients, (2) the use of a group intervention effectively increased the required sample size by 50%, (3) similarity of randomization rates suggests that generalizability of study results will probably be comparable to that of other randomized cancer trials, (4) multidisciplinary collaborations and involvement of experienced researchers facilitated enrollment, and (5) most challenges encountered in recruitment were similar to those seen in all clinical trials.

Breast Neoplasms↗

High-dose cytosine arabinoside in the treatment of acute myeloid leukemia: Review of three randomized trials.

BACKGROUND: The use of high-dose cytosine arabinoside (HDAraC) during induction may improve outcomes in patients with acute myeloid leukemia (AML) compared with standard-dose AraC (SDAraC). The objective of this review was to assess the impact of HDAraC during induction therapy for patients with AML based on results from randomized trials. METHODS: All randomized trials in the field were identified by using a predefined search strategy. Trials that assessed the impact of HDAraC compared with SDAraC as induction therapy for adult patients with AML in a randomized fashion and that reported the relevant endpoints were included. Data were extracted from each trial by both reviewers according to prespecified criteria. RESULTS: No differences between HDAraC and SDAraC were found with regard to complete remission rates (relative risk, 1.00; 95% confidence interval [95% CI], 0.92-1.10). The weighted mean difference (WMD) for median recurrence-free survival (RFS) was 4.19 in favor of HDAraC (95% CI, 0.59-7.78; P = .02). The WMD for 4-year RFS was 10.98 in favor of HDAraC (95% CI, 1.02-20.94; P = .03). The WMD for median overall survival (OS) was - 0.22 for HDAraC compared with SDAraC (95% CI, - 2.76-2.32; P = .9). Data regarding the median OS was heterogeneous between studies (chi-square P = .00), with 2 studies in favor of HDAraC and 2 studies in favor of SDAraC. The WMD for 4-year OS was 6.21 in favor of HDAraC (95% CI, 2.70-9.72; P = .0005). CONCLUSIONS: Induction therapy with HDAraC improved long-term disease control and overall survival in adults age < 60 years with de novo AML. It remains unknown whether patients should receive HDAraC during induction or if it is to be given during postremission therapy. Further analyses should focus on this issue and on the effects of HDAraC in prognostically different subgroups of patients with AML.

Adolescent↗

A randomized trial of burch retropubic urethropexy and anterior colporrhaphy for stress urinary incontinence.

OBJECTIVE: In a randomized trial, we compared the success of Burch retropubic urethropexy to the modified anterior colporrhaphy for the treatment of genuine stress urinary incontinence. METHODS: Thirty-five patients with stress incontinence were randomly assigned to undergo Burch retropubic urethropexy or modified anterior colporrhaphy. Subjects had preoperative and 1-year postoperative physical examinations, multichannel urodynamic testing, 20-minute pad test, and subjective grading of incontinence severity with questionnaires. Data were evaluated using Fisher exact test, Wilcoxon two-sample test, logistic regression analysis, and analysis of variance. RESULTS: Objective cure 1 year postoperatively was significantly greater for the women treated by Burch retropubic urethropexy than by modified anterior colporrhaphy (16 of 18 [89%] versus five of 16 [31%], relative risk .15, 95% confidence interval .04, .59). Patients' subjective ratings of incontinence severity 1 year after surgical treatment were significantly lower in women who had Burch retropubic urethropexy. CONCLUSION: Burch retropubic urethropexy yields a significantly superior objective cure for genuine stress urinary incontinence than the modified anterior colporrhaphy in a randomized trial.

Adult↗

Race and survival of men treated for prostate cancer on radiation therapy oncology group phase III randomized trials.

PURPOSE: We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials. MATERIALS AND METHODS: Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively. RESULTS: On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA. CONCLUSIONS: As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

Black or African American↗

A randomized trial of fistulotomy in perianal abscess.

In a randomized trial we compared the treatment of perianal abscess by incision only (18 patients) with that by incision followed by fistulotomy 3 days later (20 patients). All patients were observed for 12 months. There were no differences between the two groups with regard to recurrent abscess/fistula, but the fistulotomy group had a statistically significantly higher prevalence of flatus incontinence. Further, fistulotomy was followed by significantly longer duration of hospitalization and by delayed healing. We recommend that fistulotomy is used only in patients with recurrent abscess.

Abscess↗

Antithrombotic therapy in atrial fibrillation: a review of randomized trials with special reference to the Stroke Prevention in Atrial Fibrillation II (SPAF II) Trial.

Nonvalvular atrial fibrillation is common and is associated with a high risk of system embolism. Recently, several large randomized trials have been completed that have established the efficacy of antithrombotic therapy for both primary and secondary prevention of systemic thromboembolism with an acceptable rate of bleeding complications in these patients. This section of clinical trials review summarizes data from all published randomized trials of antithrombotic therapy in atrial fibrillation. The efficacy of aspirin versus warfarin is analyzed. The role of clinical and echo-cardiographic findings to stratify patients is also highlighted. The Stroke Prevention in Atrial Fibrillation II trial is discussed in detail.

Atrial Fibrillation↗

Scientific challenges in the application of randomized trials.

In recent years, scientific challenges in the application of randomized trials have become more apparent, especially with the extension of such trials to the assessment of nondrug treatments, such as health education, psychotherapy, and health care provision. Six issues (individual v group randomization, blinding and unblinding, the effect of trial participation on outcome, selective subject participation, treatment compliance, and standardized v individualized treatment) are discussed in terms of their impact on internal validity, generalizability (external validity), and clinical relevance. Specific design strategies may be necessary to enhance these methodological and clinical desiderata. Attention to these challenges should lead to improvements in future randomized trials.

Attitude↗

Randomized trial of choledochocholedochostomy with or without a T tube in orthotopic liver transplantation.

OBJECTIVE: To compare the incidence of biliary complications after liver transplantation in patients undergoing choledochocholedochostomy reconstruction with or without T tube in a multicenter, prospective, randomized trial. SUMMARY BACKGROUND DATA: Several reports have suggested that biliary anastomosis without a T tube is a safe method of biliary reconstruction that could avoid complications related to the use of T tubes. No large prospective randomized trial has so far been published to compare the two techniques. METHODS: One hundred eighty recipients of orthotopic liver transplantation were randomly assigned to choledochocholedochostomy with (n = 90) or without (n = 90) a T tube in six French liver transplantation centers. All types of biliary complications were taken into account. RESULTS: The overall biliary complication rate was increased in the T-tube group, even though these complications did not lead to an increase in surgical or radiologic therapeutic procedures. The major significant complication was cholangitis in the T-tube group; this did not occur in the other group. The incidence of biliary fistula was 10% in the T-tube group and 2.2% in the group without a T tube. Other biliary complications were similar. The complication rate of cholangiography performed with the T tube was greater than with other types of biliary exploration. The graft and patient survival rates were similar in the two groups. CONCLUSION: This study is the first large prospective, randomized trial of biliary complications with or without a T tube. The authors found an increase in the biliary complication rate in the T-tube group, which was linked to minor complications. The T tube did not provide a safer access to the biliary tree compared with the others types of biliary explorations. The authors recommend the performance of choledochocholedochostomy without a T tube in liver transplantation.

Adolescent↗

[Requirements for the randomized trial of i.a. vs. i.v. administration to reveal the impact of hepatic arterial infusion on survival in the treatment of liver metastases].

In spite of its high response rate, the impact of hepatic arterial infusion (HAI) chemotherapy on survival is still uncertain in the treatment of liver metastases. There were no significant differences in survival between i.a. and i.v. in western randomized trials for liver metastases from colorectal cancer in the 1980s. The requirements for randomized trials between i.v. and i.a. administration for liver metastases to reveal the impact of HAI on survival are as follows. 1) Investigators have standardized the technical level for HAI. 2) The natural history of the disease is not so long for continuing HAI over living period. 3) The cases have no extra-hepatic lesions. 4) The number of patients suffices for the evaluation. Therefore, the patients with liver metastases from gastric cancer and without extra-hepatic lesions are better materials for the randomized trial of i.a. vs i.v. in Japan, and the multiinstitutional trial with standard technical level is recommended.

Antineoplastic Combined Chemotherapy Protocols↗

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: results of a prospective randomized trial.

Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P =.01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P = not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT.

Animals↗

Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data.

BACKGROUND: Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events. METHODS AND RESULTS: A systematic review was performed of publications since 1980. For inclusion, trials had to compare an atrial-based with a ventricular-based pacing mode; use a randomized, controlled, parallel design; and have data on mortality, stroke, heart failure, or atrial fibrillation. Individual patient data were obtained from 5 of the 8 identified studies, representing 95% of patients in the 8 trials, and a total of 35 000 patient-years of follow-up. There was no significant heterogeneity among the results of the individual trials. There was no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P=0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P=0.15) with atrial-based pacing. There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P=0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P=0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing. CONCLUSIONS: Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death. However, atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke.

Arrhythmias, Cardiac↗

Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen, which binds to estrogen receptors, is widely used as adjuvant therapy after surgery for early-stage breast cancer. Our previous randomized trial of adjuvant tamoxifen therapy for breast cancer showed a significant decrease of new, contralateral breast cancers in patients who received tamoxifen. Tamoxifen may also influence risk factors for cardiac and thromboembolic disease (e.g., serum cholesterol and antithrombin III). PURPOSE: The purpose of this study was to assess morbidity from cardiac and thromboembolic disease among 2365 postmenopausal patients with early-stage breast cancer in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus no adjuvant endocrine therapy. Patients were entered in the study from November 1976 through December 1988. METHODS: In our retrospective study, the analysis of morbidity was based on data from a computerized, population-based register of hospital admissions and discharge diagnoses. Mortality data were obtained from the Swedish National Central Bureau of Statistics. In the Stockholm study, treatment with tamoxifen was initiated within 4-6 weeks of modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection and postoperative radiation therapy to the breast. In that randomized trial, 755 patients at low risk of death from breast cancer received adjuvant tamoxifen only; 760 received no treatment. In addition, 628 high-risk patients were randomly assigned to receive adjuvant chemotherapy plus tamoxifen (173 patients) or postoperative radiotherapy plus tamoxifen (151) or, as a control, to receive chemotherapy (171) or postoperative radiation therapy (133), both without tamoxifen or other endocrine therapy. Median follow-up was 6 years. RESULTS: Tamoxifen therapy resulted in a statistically significant reduced incidence of hospital admissions due to cardiac disease. The relative hazard (tamoxifen for 2 or 5 years versus control) was 0.68 (95% confidence interval [CI] = 0.48-0.97; P = .03). In the randomized comparison of 5 versus 2 years of tamoxifen, there was a statistically significant difference favoring the longer treatment (relative hazard = 0.37; 95% CI = 0.15-0.92; P = .03). There was little difference between the tamoxifen and control groups in terms of admissions due to thromboembolic disease. CONCLUSIONS: These findings suggest that long-term adjuvant treatment with tamoxifen may result in substantial reduction of cardiac morbidity in patients with low risk of death from breast cancer as well as in women in chemopreventive studies who have high risk of developing breast cancer. IMPLICATIONS: Our results support continuation of ongoing trials of tamoxifen therapy in these two groups of subjects.

Aged↗

Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial.

Depression is a major health problem and is not only underrecognized and undertreated but is associated with significant morbidity and mortality. Lavandula angustifolia Mill. (Lamiacae) is used to treat depression. Many medicinal plant textbooks refer to this indication, whereas there is no evidence-based document. Our objective was to compare the efficacy of tincture of L. angustifolia with imipramine in the treatment of mild to moderate depression and to evaluate the possible adjuvant effect of this tincture in a 4 week double-blind, randomized trial. Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive lavandula tincture (1:5 in 50% alcohol ) 60 drops/day plus placebo tablet (Group A), tablet imipramine 100 mg/day plus placebo drop (Group B) and tablet imipramine 100 mg/day plus lavandula tincture 60 drops/day (Group C) for a 4-week study. In this small preliminary double-blind and randomized trial, lavandula tincture at this concentration was found to be less effective than imipramine in the treatment of mild to moderate depression (F=13.16, df=1, P=.001). In the imipramine group, anticholinergic effects such as dry mouth and urinary retention were observed more often that was predictable, whereas headache was observed more in the lavandula tincture group. A combination of imipramine and lavandula tincture was more effective than imipramine alone (F=20.83, df=1, P<.0001). As this study indicates, one of the advantages of this combination is a better and earlier improvement. The main overall finding from this study is that lavandula tincture may be of therapeutic benefit in the management of mild to moderate depression as adjuvant therapy. A large-scale trial is justified.

Adult↗

Treatment of panic disorder via the Internet: a randomized trial of CBT vs. applied relaxation.

A randomized trial was conducted of two different self-help programs for panic disorder (PD) on the Internet. After confirming the PD-diagnosis with an in-person structured clinical interview for DSM-IV (SCID) interview 22 participants were randomized to either applied relaxation (AR) or a multimodal treatment package based on cognitive behavioral therapy (CBT). Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail has a significant medium to large effect (Cohen's d=0.71 for AR and d=0.42 for CBT). The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.

Adult↗

A descriptive study of randomized trials of treatments for childhood acute lymphoblastic leukaemia.

This report presents a historical and descriptive account of randomized trials in childhood leukaemia since the earliest such studies in the 1960s. It focuses on trials that began before 1988, making use of the register of trials developed for a systematic review of treatments for acute lymphoblastic leukaemia in children. The number of randomized trials starting each year increased from one or two in the 1960s to an annual average of five or six in the 1980s. However trials remained relatively small, with more than half of all randomizations accruing less than 200 patients and only five having more than 1000. Most trials were published more than once.

Adolescent↗

Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women.

Studies of the effect of exercise programs on bone mass appear inconsistent. Our objective was to systematically review and meta-analyze randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. A computerized MEDLINE search was conducted for the years 1966-1997. Thirty-five randomized trials were identified. Meta-analytic methods were used to statistically pool results of studies of the effect of impact (e.g., aerobics) and non-impact (e.g., weight training) exercise on the lumbar spine and femoral neck. The most studied bone site was the lumbar spine in postmenopausal women (15 studies), where both impact [1.6% bone loss prevented, 95% confidence intervals (CI): 1.0%-2.2%] and non-impact (1.0%, 95% CI: 0.4%-1.6%) exercise programs had a positive effect. Results for the lumbar spine in premenopausal women (eight studies) were similar: 1.5% (95% CI: 0.6%-2.4%) less bone loss (or net gain) after impact exercise and 1.2% (95% CI: 0.7%-1.7%) after non-impact exercise. Impact exercise programs appeared to have a positive effect at the femoral neck in postmenopausal women (five studies), 1.0% (95% CI: 0.4%-1.6%) bone loss prevented, and possibly in premenopausal women, 0.9% (95% CI: -0.2%-2.0%) bone loss prevented. There were too few trials to draw conclusions from meta-analyses of the effect of non-impact exercise on the neck of femur. This systematic review of randomized trials shows that both impact and non-impact exercise have a positive effect at the lumbar spine in pre- and postmenopausal women. Impact exercise probably has a positive effect at the femoral neck. More studies are required to determine the optimal intensity and type of exercise.

Animals↗