Significant Difference In Adverse Effects Research Articles

Double-Blind Prospective Comparative Trial between Foamed and Liquid Polidocanol and Sodium Tetradecyl Sulfate in the Treatment of Varicose and Telangiectatic Leg Veins

Background Twenty subjects were treated with either polidocanol (POL) or sodium tetradecyl sulfate (STS) to compare the efficacy and adverse sequelae of each agent. Objective To determine the safety and efficacy of two widely used sclerosing agents. Methods After the exclusion of saphenofemoral junction incompetency, each subject's leg veins were categorized by size (< 1, 1–3, and 3–6 mm in diameter). Each leg was then randomized to be treated with 0.5%, 1%, or 1% foam of POL or 0.25%, 0.5%, or 0.5% foam of STS according to vein size. An independent panel of four physicians, blinded to treatment, performed randomized photographic evaluations obtained pretreatment and 12 weeks post-treatment. Subject satisfaction index and overall clinical improvement assessment were also obtained. Results An average 83% improvement was noted for all vein sizes in all subjects with both POL and STS after a single treatment. Subjects were satisfied with treatment, regardless of the sclerosing agent used or the vein size treated. There was no statistically significant difference in adverse effects between each group. Conclusion Both POL and STS are safe and effective sclerosing agents in the treatment of varicose and telangiectatic leg veins. Both are very tolerable and demonstrate similar post-treatment sequelae.

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. We supplemented past searches of Current Controlled Trials (10/2000), the Cochrane Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an update search of the Cochrane Schizophrenia Group's Register of trials (September 2003). All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. Data were extracted independently by two reviewers and cross-checked. We calculated fixed effects relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. Where possible, the number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by intention-to-treat. Mean differences were used for continuous variables. We found no data for the primary outcome, tranquilisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1 RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49 CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1 RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n=148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (<20%). Three studies found no difference in the proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24 hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at 24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Well-conducted pragmatic randomised controlled trials are needed.

Efficacy of IV Theophylline in Children with Severe Status Asthmaticus

Purpose of the Study. To determine if the addition of intravenous (IV) theophylline to an aggressive treatment regimen of inhaled and IV beta-agonists, inhaled ipratroprium and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric intensive care unit (PICU).Study Population. Forty-seven children with a diagnosis of status asthmaticus who were admitted to the Cardinal Glennon Children’s Hospital in St Louis PICU for ≤2 hours. All subjects were in severe distress with a modified Wood-Downes clinical asthma score (CAS) of ≥5. Subjects’ age range was 13 months to 17 years.Methods. Subjects were enrolled who fulfilled the above criteria. In brief, the CAS includes measures of oxygenation, breath sounds, accessory muscle use, expiratory wheezing, and cerebral function. Admission to the PICU was determined by inadequate response to repeated albuterol treatments and the ED and critical care staff. Subjects were randomly assigned to receive in addition to their regular aggressive treatment (denoted above in purpose of study) either IV aminophylline 7 mg/kg loading dose followed by age adjusted rates of 0.5–0.65 mg/kg/hr or no additional treatment (controls). Theophylline levels were kept between 12 to 17 μg/mL. The CAS evaluations were performed by investigators blinded to the treatment and were performed twice daily by 1 of 4 investigators. The PICU attending and resident team were all aware of the treatment assignment and made all medical decisions related to the subjects. CAS was suspended in the event of intubation and resumed on extubation. Nursing staff was queried regarding side effects of the subjects.Results. There was no significant difference between the theophylline and control groups with respect to age, sex, race, home medications, past use of hospital resources, origin (ED or ward), ED treatment, or time of admission. The baseline CAS scores were not different. Six subjects required mechanical ventilation (3 in each group), although the 3 control subjects were intubated after treatment and the 3 in the theophylline group before treatment was begun. Subjects receiving IV theophylline had a significant decrease in time to reach CAS ≤3 and a greater percentage change in respiratory rate than control subjects during the first 12 hours in the PICU. Theophylline did not significantly influence the time to meet PICU discharge criteria among patients not receiving mechanical ventilation, but in those requiring intubation, the PICU stay was reduced. There was no significant difference in adverse effects between the 2 groups, except and increase in complaints of emesis in the theophylline group and increase in tremor in the control group.Conclusions. Contrary to the National Heart Lung and Blood Institute guidelines for treatment of status asthmaticus in children, this study suggests that critically ill children with severe status asthmaticus may benefit from the addition of IV theophylline to β-agonist, anticholinergic, and corticosteroid therapies. Additional studies may examine the administration of theophylline to select patients in the ED unresponsive to conventional therapy or in patients known to be high risk for respiratory failure.Reviewer’s Comments. This is the first prospective randomized trial of IV theophylline limited to children admitted to the PICU. Other studies in hospitalized (noncritical care) asthmatic children failed to show a benefit with the addition of theophylline to conventional treatment. It is possible that the benefit of the addition of theophylline is dependent on the severity of their illness. Adult studies have shown the improvement in spirometry with the addition of a methylxanthine is related to the degree of airway narrowing. The addition of theophylline may serve to reduce the incidence of respiratory failure and mechanical ventilation in children with severe status asthmaticus. The authors note that not blinding the medical team to the treatment may have influenced the results to some degree, but for safety reasons, they did not feel that was warranted. The authors referred to this as a “controlled” study, but there was no reference to a placebo (ex: saline). It would be interesting to repeat this study with a placebo control and with some of the newer critical care treatments such as heliox.

Crystalloids, colloids and kids: a review of paediatric burns in intensive care

This is a retrospective review of all burns patients admitted to a paediatric intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and clinical course are presented. Ninety-eight new burns victims were admitted with a mortality rate of 10.2%, all in burns of greater than 25% body surface area (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients with burns greater than 5% BSA, 33 received the hospital-recommended colloid-based resuscitation formula, 46 received a combination of crystalloids and colloids and in 6 patients the resuscitation regimen was not able to be determined. The aetiology, age distribution, sex ratio, severity of burns and length of stay in hospital did not alter significantly over the study period. The number of burns admissions to PICU increased, as did their duration of intubation and ICU stay. The hospital-recommended resuscitation formula consistently underestimated the fluid volume required for adequate resuscitation. No statistically significant difference in adverse effects was found between the resuscitation groups. This study is unable to recommend a definitive approach to the fluid resuscitation of burns shock in paediatrics and the best approach is one of meticulous fluid resuscitation titrated on clinical effect.

Adverse events and cost savings three years after implementation of guidelines for outpatient contrast-agent use.

The ability of guidelines limiting the use of low-osmolality contrast media (LOCM) to save money without jeopardizing patient care was studies. In February 1993 an academic medical center implemented guidelines to reduce the use of LOCM for outpatient computed tomography and excretory urography; the guidelines limited LOCM to patients at high risk of adverse reactions to contrast agents. Data on contrast media received and frequency of adverse events were compiled from billing sheets and incident reports for March 1993 through February 1996. The number of patients receiving LOCM over the three years was 1325, and the number receiving high-osmolality contrast media (HOCM) was 4435. Of the HOCM recipients, 165 (3.7%) had adverse reactions; 0.4% of these reactions were major, 3.1% were minor, and 0.2% were extravasations. Among LOCM-treated patients, 35 (2.7%) had adverse reactions; 0.5% were major, 1.7% were minor, and 0.5% were extravasations. The only significant difference in adverse effects between the groups was in the frequency of minor reactions. The costs of HOCM and LOCM over the three years were $54,660 and $152,523, respectively. Had 90% of the 5760 patients received LOCM, the total cost of contrast agents would have been $603,723; thus, the estimated drug cost saving was $396,540, or $132,180 annually. With costs of treating adverse events factored in, the net annual cost saving was $132,093. Guidelines limiting the use of LOCM to high-risk patients saved an academic medical center an estimated $132,093 annually in drug costs for specific outpatient imaging procedures, without adversely affecting patient care.

Single-Dose Actinomycin D in the Treatment of Postmolar Trophoblastic Disease

In 1980 Petrilli and Morrow compared the toxicity of actinomycin D given in five daily doses with the toxicity of a larger single dose in a biweekly treatment schedule for gestational trophoblastic disease. They found no significant difference in adverse effects and concluded that further study of this single dose regimen was in order.