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Evaluation of health status in epilepsy using the EQ-5D questionnaire: a prospective, observational, 6-month study of adjunctive therapy with anti-epileptic drugs.

AIMS: The aims of this project were to evaluate the impact of adjunctive treatment with an anti-epileptic drug (AED) on the health status of people with epilepsy and to investigate how seizure frequency affects their health status. METHODS: Adult epilepsy patients, refractory to current treatment, were included in this prospective observational study. Patients commencing adjunctive therapy with one of five AEDs (topiramate, lamotrigine, gabapentin, clobazam, vigabatrin) were eligible for inclusion. The study took place at the outpatient clinics of the National Hospital for Neurology and Neurosurgery, Queen Square, London. Patients completed the EQ-5D, a generic health status measure, at baseline and again after 3 and 6 months. Information was also collected on medications and seizure frequency. RESULTS: In total, 125 patients entered the study and were followed up for 6 months. Patients treated with topiramate had a significant increase (p < 0.05) in EQ-5D score from baseline, indicating an improvement in their health status whereas scores for lamotrigine, clobazam and gabapentin all showed a non-significant decline. When the data were analysed according to seizure frequency, only patients who became seizure-free on adjunctive treatment had a significant increase in their health status. The group who had a 50% reduction in seizure frequency did not have increased health status. CONCLUSIONS: In summary, adjunctive treatment with topiramate significantly increased health status as measured by the EQ-5D. These data also suggest that achievement of seizure-freedom is the key to improving health status in this patient group.

Adult↗

Acupuncture as adjunctive therapy in assisted reproduction: remaining uncertainties.

Two randomized trials provide suggestive evidence that acupuncture might be an effective adjunctive therapy in assisted reproductive technologies, leading to improved pregnancy rates. However, additional research addressing remaining scientific and methodologic issues is needed before routine use of acupuncture can be recommended.

Acupuncture↗

Efficacy of bunazosin hydrochloride 0.01% as adjunctive therapy of latanoprost or timolol.

PURPOSE: To evaluate the ocular hypotensive response of bunazosin hydrochloride 0.01% administered as adjunctive therapy in patients with glaucoma who were already receiving latanoprost 0.005% or timolol 0.5%. METHODS: Patients with primary open angle glaucoma who had received latanoprost (n = 60) or timolol (n = 60) for 6 months or longer were enrolled and prospectively randomized to receive additional administration of bunazosin or placebo. One hundred twenty eyes of 120 patients were thus divided into 4 subgroups of 30 patients each. Bunazosin was administered twice daily, and timolol or latanoprost was administered per label. The patients were followed up for 3 months. Responders were defined as having a reduction in intraocular pressure of greater than 2 mm Hg from baseline. RESULTS: Mean baseline intraocular pressure was 22.3 +/- 3.0 mm Hg in the bunazosin subgroup and 22.3 +/- 3.1 mm Hg in the placebo subgroup of the latanoprost arm, and 22.5 +/- 3.5 mm Hg in the bunazosin subgroup and 22.3 +/- 3.0 mm Hg in the placebo subgroup of the timolol arm. In the bunazosin subgroups of both arms, intraocular pressure was significantly reduced compared with baseline measurements (P < 0.05) with mean intraocular pressure measurement reductions of 2.1 +/- 2.4 mm Hg and 2.8 +/- 2.1 mm Hg in the latanoprost arm and 2.6 +/- 2.1 mm Hg and 2.8 +/- 2.1 mm Hg in the timolol arm at 6 and 12 weeks after the start of the follow-up, respectively. In the latanoprost group, bunazosin provided a further reduction of intraocular pressure (7.7%) at 12 weeks from that initially obtained at 2 weeks (P = 0.0377). In the placebo subgroups of the latanoprost and timolol arms, no significant change was found between at baseline and at any visit after the start of the follow-up. In the latanoprost and timolol arms, there was a significant difference in intraocular pressure and its change between the bunazosin subgroup and placebo subgroup at any visit after 4 weeks from the start of the follow-up (P < 0.01). CONCLUSION: Bunazosin hydrochloride 0.01% may provide an additional intraocular pressure reduction in patients already receiving latanoprost or timolol. Since adding bunazosin to eyes treated with latanoprost caused a relatively small hypotensive response at 2 weeks and provided a further reduction from 2 weeks to 12 weeks, longer than 4 weeks may be required to evaluate a clinically meaningful response to treatment. Further investigation on more cases and longer follow-up are needed.

Adrenergic alpha-Antagonists↗

Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis.

To ascertain the role of total enteral nutrition, compared with total parenteral nutrition, as adjunct therapy to steroids in patients with severe acute ulcerative colitis, a prospective randomized trial was conducted in 42 of such patients. Inclusion criteria were the persistence of a moderate or severe attack of the disease (Truelove's index) after 48 h on full steroid treatment (prednisone 1 mg/kg/day). Patients were randomized to receive polymeric total enteral nutrition or isocaloric, isonitrogenous total parenteral nutrition as the sole nutritional support. Remission rate and need for colectomy were similar in both groups. No significant changes in anthropometric parameters were observed in either nutritional group at the end of the study. Median increase in serum albumin was 16.7% (-0.5% to +30.4%) in the enteral feeding group, and only 4.6% (-12.0% to +13.7%) in the parenteral nutrition patients (p = 0.019). Adverse effects related to artificial nutritional support were less frequent (9% vs. 35%, p = 0.046) and milder in enterally fed patients. Postoperative infections occurred more often with parenteral nutrition (p = 0.028). These results suggest that total enteral nutrition is safe and nutritionally effective in severe attacks of ulcerative colitis. It is also cheaper and associated with fewer complications than parenteral nutrition. Total enteral nutrition should be regarded as the most suitable type of nutritional support in these patients.

Acute Disease↗

Role of new anticoagulants as adjunctive therapy during thrombolysis.

Procoagulant activity may persist during coronary thrombolysis and result in either delay in the time to recanalization or recurrent thrombosis. Although heparin and aspirin form the mainstay of current therapy, recurrent thrombosis occurs despite adjunctive heparin therapy during thrombolysis. Newer agents that inhibit thrombin by antithrombin III-independent mechanisms, or that inhibit earlier steps in the coagulation cascade, have been shown to be effective in the experimental preparation of coronary thrombolysis. Because heparin-antithrombin III is a relatively inefficient inhibitor of thrombin bound to fibrin, agents such as hirudin or small peptide inhibitors of the thrombin-active site appear to be more effective inhibitors of clot-associated thrombin activity. Inhibition of early steps in the coagulation cascade with the inhibitor of tissue factor-factor VIIa complex, or with activated protein C, also appears to be an effective anticoagulant strategy. In experimental preparations all of these agents have shown superiority in preventing recurrent thrombosis compared with heparin, and in some cases they appear to accelerate the rate of clot lysis.

Anticoagulants↗

High-frequency oscillatory ventilation and adjunctive therapies: inhaled nitric oxide and prone positioning.

OBJECTIVE: To review the use of high-frequency oscillatory ventilation (HFOV) with adjunctive therapies (inhaled nitric oxide [iNO] and prone positioning [PP]) in adult patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: Published studies evaluating the use of iNO, PP, and HFOV in adult patients with ARDS. DATA SUMMARY: Despite ongoing preclinical and clinical research, the therapeutic armamentarium for ARDS remains limited. Although a pressure- and volume-limited strategy aimed at mitigating ventilator-associated lung injury has demonstrated mortality benefit, patients with severe ARDS may still develop life-threatening hypoxemia. As a result, various salvage therapies aimed at improving oxygenation, including HFOV, iNO, and PP alone or in combination, have been evaluated in patients with refractory ARDS. Although the few preclinical and clinical trials of combination therapy to date have shown promising improvements in oxygenation and other physiological variables, with few adverse clinical events, the impact on survival awaits the performance of large randomized trials. CONCLUSIONS: There is limited clinical data to recommend the widespread use of combination therapy in patients with ARDS. In the subset of patients with life-threatening hypoxemia from refractory ARDS, combination therapy is safe and may be considered for salvage therapy. More rigorous randomized, controlled trials are needed to help delineate the therapeutic role of combination therapy in adults with ARDS.

Administration, Inhalation↗

Oxcarbazepine adjunctive therapy in infants and young children with partial seizures.

OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of oxcarbazepine as adjunctive therapy in infants and young children (1 month to < 4 years). METHODS: Children 1 month to < 4 years of age with inadequately controlled partial seizures taking up to two concomitant antiepileptic drugs (AEDs) were enrolled in this rater-blind, randomized, parallel-group study. Patients received either high-dose (60 mg/kg/day) or low-dose (10 mg/kg/day) oxcarbazepine as oral suspension. The primary efficacy variable was the absolute change in electrographic partial seizures with a behavioral correlate (type 1 seizure) frequency per 24 hours during the last 72 hours of continuous video-EEG monitoring in the treatment phase compared with baseline seizure frequency. RESULTS: Of 191 patients screened, 128 were randomized: 64 to both oxcarbazepine dose groups. The median absolute change in type 1 seizure frequency per 24 hours was more effective for the high-dose group (-2.00) compared with the low-dose group (-1.37; p = 0.043). The median percentage reduction in type 1 seizure frequency per 24 hours was also greater in the high-dose group (83.33%) than in the low-dose group (46.18%; p = 0.047). The most frequent adverse events (> or = 10%) were somnolence and pyrexia, and most were mild in severity. CONCLUSIONS: In this study, high-dose oxcarbazepine was significantly more effective than low-dose oxcarbazepine in controlling partial seizures in infants and very young children.

Administration, Oral↗

Lamotrigine adjunctive therapy among children and adolescents with primary generalized tonic-clonic seizures.

CONTEXT AND OBJECTIVE: Primary generalized tonic-clonic seizures are relatively more common among children than among adults. Primary generalized tonic-clonic seizures are associated with increased risk of injury and death. Therefore, effective control of primary generalized tonic-clonic seizures is necessary to reduce epilepsy-related morbidity and mortality. Lamotrigine has demonstrated efficacy from published randomized clinical trials for childhood partial seizures, absence seizures, and for the generalized seizures associated with Lennox-Gastaut syndrome. A randomized, blinded, placebo-controlled study was conducted to assess the efficacy and tolerability of adjunctive therapy with lamotrigine in the treatment of primary generalized tonic-clonic seizures among patients > or = 2 years of age; we report the data from children and adolescents 2 to 20 years of age from this randomized clinical trial. This is the first published analysis of data from a randomized, double-blind, controlled clinical trial of primary generalized tonic-clonic seizures focusing on children and adolescents. PATIENTS AND METHODS: We randomly assigned (1:1) 117 patients, aged 2 to 55 years, with primary generalized tonic-clonic seizures inadequately controlled on 1 to 2 current antiepileptic drugs and with evidence of primary generalized tonic-clonic seizures on electroencephalogram and no historical or electroencephalogram evidence of partial seizures to either lamotrigine or placebo in a double-blind parallel group clinical trial from 2001 through 2004. We analyzed the subgroup of children and adolescents, aged 2 to 20 years (n = 45), from this randomized clinical trial. Patients having > or = 3 primary generalized tonic-clonic seizures over an 8-week baseline were randomly assigned (1:1) to receive either lamotrigine or placebo. The treatment period consisted of an escalation phase (12 weeks for patients 2-12 years; 7 weeks for patients > 12 years) and a maintenance phase (12 weeks). The study had 4 phases: screening phase, baseline phase, escalation phase, and maintenance phase. During the screening phase, baseline medical examinations and seizure type and seizure frequency assessments were performed. During the 8-week baseline phase, the number and dosages of concomitant antiepileptic drugs were maintained while seizure frequency was assessed. The assessment of primary generalized tonic-clonic seizure frequency was determined during the 8-week baseline phase. Patients eligible for random assignment experienced > or =3 primary generalized tonic-clonic seizures during the baseline phase and > or = 1 primary generalized tonic-clonic seizure in the 8 weeks before the baseline phase. Lamotrigine was introduced and titrated using a schedule based on the patients' age and concurrent antiepileptic drug regimen. During the escalation phase, the number and doses of concomitant antiepileptic drugs were not changed. The escalation phase was followed by a 12-week maintenance phase during which time the lamotrigine dose was maintained at a specific dose defined by the patients' age and concomitant antiepileptic drugs, whereas the doses of concurrent antiepileptic drugs were maintained at a constant dose. Concurrent antiepileptic drugs could not be discontinued or added during the maintenance phase. The primary efficacy end point measure was the median reduction in the frequency of primary generalized tonic-clonic seizures from baseline; seizure counts were recorded prospectively in standardized daily seizure diaries. Other efficacy end point data for analysis were as follows: the median seizure counts, the median percentage change from the baseline phase in average monthly seizure frequency for other generalized seizure types, and the percentage of patients with a reduction of > or = 25%, > or = 50%, > or = 75%, or 100% in frequencies of primary generalized tonic-clonic seizures and all generalized seizures during the escalation phase and/or maintenance phase relative to the baseline phase. Accurate counts of absence seizure frequency require electroencephalogram-video monitoring; absence seizure frequency was not an outcome measure for this analysis. RESULTS: Forty-five (21 lamotrigine and 24 placebo) patients 2 to 19 years of age were randomly assigned and received study drug. Eight patients (3 lamotrigine and 5 placebo) had a combination of clinical (myoclonus and/or absence seizures) and electroencephalogram findings that were consistent with juvenile myoclonic epilepsy. Among the 45 children randomly assigned, 74% had generalized spike, polyspike, and/or generalized spike and wave discharges on routine electroencephalogram recordings; the remaining 26% of children had no electroencephalogram findings suggestive of partial epilepsy and a clear history consistent with primary generalized tonic-clonic seizures. Electroencephalogram findings were not significantly different between the lamotrigine and the placebo treatment groups. The median percentage decrease from baseline in primary generalized tonic-clonic seizures during the entire treatment period was 77% in the lamotrigine group and 40% in the placebo group (P = .044). The median primary generalized tonic-clonic seizure counts per month were 0.7 in the lamotrigine group and 3.6 in the placebo group during escalation (P = .008), 0.3 in the lamotrigine group and 2.0 in the placebo group during maintenance (P = .005), and 0.4 in the lamotrigine group and 2.5 in the placebo group during the entire treatment period (P = .007). Trends were noted during escalation and maintenance with a median percentage decrease in primary generalized tonic-clonic seizures during escalation of 72% in the lamotrigine group and 30% in the placebo group (P = .059), and 83% in the lamotrigine group and 42% in the placebo group during maintenance (P = .058). During the maintenance phase, 48% of lamotrigine patients were seizure free compared with 17% treated with placebo (P = .051). One patient from each treatment group discontinued from the study because of an adverse event; 1 patient who received lamotrigine experienced "disorientation"; and 1 patient who received placebo had a convulsion with apnea. No rashes occurred among patients taking lamotrigine or placebo. No patient experienced worsening of the intensity or frequency of myoclonus. CONCLUSIONS: Adjunctive lamotrigine therapy seems effective in controlling primary generalized tonic-clonic seizures among patients 2 to 20 years of age.

Adolescent↗

Adjunctive therapy in epilepsy: a cost-effectiveness comparison of alternative treatment options.

A pharmaco-economic study of the administration of adjunctive therapy in patients with chronic epilepsy is described. A decision-analytic model has been used, which represents the consequences of treatment over a 1-year time period, when one of three drugs is used first. The cost-effectiveness ratio for clobazam, lamotrigine and vigabatrin have been calculated. The expected cost per patient of treatment over the 1-year period was up to 50% higher with vigabatrin and lamotrigine compared with clobazam, with a cost-effectiveness ratio around 40% higher.

Acetates↗

Low-dose dexamethasone as adjunctive therapy for disseminated Mycobacterium avium complex infections in AIDS patients.

Five human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex infection had progressive weight loss and persistent fever despite multidrug antimycobacterial therapy. These patients were given daily low-dose oral dexamethasone (typically 2 mg/day) as adjunctive therapy. All had substantial and sustained weight gain (12 to 50% of pre-steroid treatment body weight [P < 0.03]), reduction in fever, and an improved sense of well-being. The serum albumin level increased during dexamethasone therapy (from 3.06 +/- 0.59 g/dl [mean +/- standard deviation] to 3.9 +/- 0.22 g/dl [P < 0.01]), while the serum alkaline phosphatase level fell (from 368 +/- 247 U/liter to 128 +/- 43.6 U/liter [P < 0.04]). Further studies of the potential role for corticosteroids in the management of disseminated M. avium complex infections in human immunodeficiency virus-infected patients are warranted.

AIDS-Related Opportunistic Infections↗

Pathogenesis-oriented targets for adjunctive therapy.

The outcome of patients with sepsis arises from multiple factors affecting both the host and the invading microorganisms. Even within the setting of adequate antimicrobial use, patients still die of sepsis. Thus, strategies focusing on further therapy targets are an important area of interest for basic and clinical research. Although such adjunctive sepsis therapy has failed to achieve consistent better survival rates so far, the progress in understanding of the pathophysiology of sepsis seen in recent years is so profound, that the possibility that a new and effective treatment may arise should be warmly considered. Indeed, it may be considered that efficacious interventions, such as early and vigorous fluid replacement, strict blood glucose control, low-dose corticosteroid reposition, protective mechanical ventilation and activated-protein C are pathogenic-oriented targets of therapy. In this paper we aim to review some aspects of the pathogenesis of sepsis, focusing on possible targets for adjunctive therapy. Published clinical trials and experimental data supporting such trials are commented on.

Animals↗

Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar disorder.

The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.

Adult↗

Contingent methadone take-home doses reinforce adjunct therapy attendance of methadone maintenance patients.

Two studies utilized within-subjects designs to determine whether take-home methadone doses can reinforce adjunct therapy attendance of drug abuse patients. These studies varied the reinforcement density and the schedule of methadone take-home doses. In Study 1, patients (n = 10) either could or could not receive a take-home following each therapy session. Study 2 patients (n = 15) could either earn take-homes following each therapy session attended (i.e., 2 take-homes per week) or could earn one take-home dose following each attendance to two consecutive sessions attended. In both studies experimental conditions alternated during three-week blocks of time. Across studies, any reinforcement by take-home doses produced more attendance at therapy sessions than that observed in the no reinforcement condition. Take-home incentive effects were strongest when each of the two weekly therapy sessions was reinforced by a methadone take-home dose. Increased attendance was not associated with reduced drug use, due perhaps to high rates of pre-study drug use and limited therapy duration. Contemporary opioid abusers present with multiple problems that methadone was never intended to treat. The present studies illustrate a method by which methadone treatment can improve the likelihood of delivering other services that may prove effective in treating some of these problems.

Adult↗

Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial.

OBJECTIVES: This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks. BACKGROUND: Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans. METHODS: In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function. RESULTS: Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo. CONCLUSIONS: A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.

Administration, Oral↗

[The effectiveness of steroid as adjunctive therapy in the management of two patients with febrile reaction due to antituberculous drugs].

Antituberculous treatment could be continued by using steroid as adjunctive therapy in two patients showing febrile reaction to antituberculous drugs in spite of desensitization therapy. Case 1 (39-year-old man) was admitted to our hospital with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest X-ray. He showed fever of 38-39 degrees C after 8 days of HREZ treatment. Desensitization therapy of RFP with the combined use of prednisolone was enforced, since the exothermic reaction continued in spite of stopping the 4 medicines, and the treatment became possible. Case 2 (40-year-old woman) was admitted with positive sputum-smear and bilateral cavitary tuberculosis (b II 2) on chest X-ray. The administration of drugs was stopped as temperature rose to 38-39 degrees C after 12 days of HREZ treatment. Though the DLST of INH was positive, the treatment with INH became possible by the combined use of PSL.

Adult↗

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy in relapsed Hodgkin disease.

OBJECTIVE: To determine the clinical and economic effects of granulocyte macrophage colony-stimulating factor (GM-CSF) as adjunct therapy in relapsed or refractory Hodgkin disease. DESIGN: A randomized, double-blind, phase III clinical trial. SETTING: A tertiary referral center. PATIENTS: Twenty-four patients (twelve of whom were controls) treated with high-dose chemotherapy and autologous bone marrow transplantation. MAIN RESULTS: The 12 patients treated with GM-CSF, when compared with placebo recipients, had shorter periods of neutropenia (median duration of an absolute neutrophil count of less than 1000 cells/mm3, 16 days compared with 27 days; P = 0.02), shorter periods of platelet-transfusion dependency (median duration, 13.5 days compared with 21 days; P = 0.03), and shorter hospitalizations (median hospital stay, 32 days compared with 40.5 days; P = 0.004). Other clinical outcomes, such as frequency and severity of toxicities, development of pneumonia or infection, in-hospital death, and response rate were similar in the two groups. Actuarial long-term disease-free survival was 64% for patients treated with GM-CSF and 58% for patients who received placebo after 32 months of follow-up (P = 0.15). The group treated with GM-CSF had lower total charges after infusion of autologous marrow than the placebo group (median in-hospital charges, $39,800 compared with $62,500; P = 0.005) because of lower post-infusion charges for room and board, antibiotic therapy, transfusions, laboratory tests, and physical therapy visits. CONCLUSIONS: Administration of GM-CSF was associated with acceleration of myeloid and platelet recovery and was cost effective in the treatment of patients with relapsed Hodgkin disease who received intensive chemotherapy.

Actuarial Analysis↗

Efficacy of brimonidine 0.2 per cent as adjunctive therapy to beta-blockers: a comparative study between POAG and CACG in Asian eyes.

OBJECTIVE: To compare the efficacy and safety profile of brimonidine as adjunctive therapy to beta-blockers between primary open angle glaucoma (POAG) and chronic angle closure glaucoma (CACG) in Asian eyes. DESIGN: Three-months, open-label, prospective study. PARTICIPANTS: Twenty-three patients (35 eyes) with POAG and 25 patients (39 eyes) with CACG were enrolled in the study. INTERVENTION: Patients with POAG or CACG post iridectomy whose IOP was inadequately controlled with topical beta-blocker monotherapy were included. Then, brimonidine 0.2 per cent was added twice daily in both groups. Study visit occurred at weeks 2, 4, 8, and 12. Complete ophthalmic examinations were performed in all visits. MAIN OUTCOME MEASURES: Efficacy was determined by reduction in IOP from baseline and tolerability was assessed by reports of adverse events. RESULTS: After 3 months of brimonidine adjunctive treatment, the mean (+/- SEM) IOP reduction were 4.37+/-0.34 mmHg (19.4%) in POAG and 4.54+/-0.37 mmHg (20.1%) in CACG (p= 0.741). No serious ocular or systemic adverse event was reported. CONCLUSION: Brimonidine was well tolerated, efficacious and provided additive IOP reduction in POAG and CACG.

Adrenergic alpha-Agonists↗

Adjunctive therapies in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for adjunctive therapies in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: Glycemic control (maintenance of glucose <150 mg/dL) is recommended. The beneficial effect of glycemic control appears to be related control of glucose and not the administration of insulin. Glycemic control should be combined with a nutritional protocol. The dialysis dose is important in sepsis-induced acute renal failure. Continuous hemofiltration offers easier management of fluid balance in hemodynamically unstable septic patients but in the absence of hemodynamic instability is equivalent to intermittent hemodialysis. It is uncertain whether high-volume hemofiltration improves prognosis in sepsis. Bicarbonate therapy is not recommended for the purpose of improving hemodynamics or reducing vasopressor requirements in the presence of lactic academia and pH >7.15.

Acidosis↗