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Intravitreal antiviral injections as adjunctive therapy in the management of immunocompetent patients with necrotizing herpetic retinopathy.

PURPOSE: To report the use of intravitreal antiviral injections as adjunctive therapy in the management of three immunocompetent patients with necrotizing herpetic retinopathy. METHOD: Case series. RESULTS: Three patients with necrotizing herpetic retinopathy received intravitreal antiviral injections for treatment of progressive retinitis, despite standard intravenous acyclovir therapy. The retinitis resolved and visual acuity improved after a minimum of 6 months of follow-up in each case. CONCLUSION: Intravitreal antiviral injections may be a safe and efficacious adjunctive therapy in the management of patients with necrotizing herpetic retinopathy.

Acyclovir↗

Microbiological response to mechanical treatment in combination with adjunctive therapy. A review of the literature.

The recognition of the microbial origin and the specificity of periodontal infections has resulted in the development of several adjunctive therapies (antibiotics and/or antiseptics) to scaling and root planing in the treatment of chronic adult periodontitis. This article aims to review the "additional" effect of a subgingival irrigation with chlorhexidine, or a local or systemic application of tetracycline or metronidazole, performed in combination with a single course of scaling and root planing in patients with chronic adult periodontitis. All treatment modalities are compared with scaling and root planing, based on their impact on: the probing depth (PD); total number of colony forming units per ml (CFU/ml); the proportions and/or the detection-frequency of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia; and/or on the percentages of cocci, spirochetes, motile, and other micro-organisms on dark field microscopy examination. All treatment modalities, including scaling and root planing without additional chemical therapy, resulted in significant reductions in the probing depth and the proportions of periodontopathogens, at least during the first 8 weeks post-therapy. However in comparison to a single course of scaling and root planing, the supplementary effect of adjunctive therapies seems to be limited. In general, only the irrigation with chlorhexidine 2%, the local application of minocycline, and the systemic use of metronidazole (in case of large proportions of spirochetes) or doxycycline (in case of large proportions of A. actinomycetemcomitans) seem to result in a prolonged supplementary effect when compared to scaling and root planing. Therefore, the use of antibiotics on a routine basis, especially in a systemic way, in the treatment of chronic adult periodontitis, can no longer be advocated, considering the increasing danger for the development of microbial resistance.

Administration, Oral↗

The role of adjunctive therapy in the management of chronic nonmalignant pain.

The management of chronic nonmalignant pain is an increasing challenge to clinicians and their patients. Adjunctive therapy, which includes a wide range of physical, psychoeducational, and multidisciplinary interventions, can play an important role in the treatment of pain. This article discusses the role and efficacy of adjunctive therapy in the management of pain associated with musculoskeletal conditions, the most common and disabling sources of chronic nonmalignant pain. Findings from meta-analyses, review articles, and recent clinical trials are reviewed that suggest that interventions that combine exercise and psychoeducational approaches designed to enhance communication, control, problem-solving, and coping can have a clinically significant impact on reducing pain and improving functional status for many conditions.

Chronic Disease↗

[Efficiency of brimonidine 0.2% and dorzolamide 2% as adjunctive therapy to beta-blockers].

PURPOSE: To evaluate the clinical efficiency and tolerability of brimonidine and dorzolamide twice daily as an adjunctive therapy for glaucoma patients with an inadequate response to beta-blockers therapy. METHODS: This multicenter prospective analysis included 92 patients (180 eyes) with primary open-angle glaucoma or ocular hypertension on therapy beta-blockers and with intraocular pressure (IOP) greater than or equal to 18mmHg. The patients were randomly treated either with brimonidine 0.2% or dorzolamide 2% added for three months. Efficiency was determined by the reduction in 15% IOP from baseline at the first and the third month. RESULTS: Mean pre-treatment IOP was 22.37 DE 2.8 mmHg in the brimonidine group and 22.38 DE 2.6 mmHg in the dorzolamide group; mean post-treatment IOP decrease was 4.39 mmHg in the brimonidine group and 3.29 mmHg in the dorzolamide group. Clinical control at the first month was achieved in 78.3% and 71% of cases respectively (p=0.05). No statistical differences existed between groups for systemic adverse events. Four patients on brimonidine discontinued treatment due to local side effects. In the dorzolamide group, two patients left the treatment referring itching and three others left due to ocular allergy. CONCLUSIONS: This study found similar efficiency and safety when treating with brimonidine or dorzolamide as an adjunctive therapy for patients with hypertension or primary open-angle glaucoma.

Adrenergic beta-Antagonists↗

A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to investigate the efficacy of acupuncture as an adjunctive therapy to standard care for the relief of pain and dysfunction in elderly patients with osteoarthritis (OA) of the knee. METHODS: Seventy-three patients with symptomatic OA of the knee were randomly assigned to treatment (acupuncture) or standard care (control). Analysis was performed on last score carried forward to account for patients who dropped out before completion. Patients self-scored Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne indices at baseline and at 4, 8 and 12 weeks. Patients in the control group were offered acupuncture treatment after 12 weeks. The data for these patients are pooled with those from the original acupuncture group for within-group analysis. RESULTS: Patients randomized to acupuncture improved on both WOMAC and Lequesne indices compared to those who received standard treatment alone. Significant differences on total WOMAC Scale were seen at 4 and 8 weeks. There appears to be a slight decline in effect at 4 weeks after cessation of treatment (12 weeks after first treatment). No adverse effects of acupuncture were reported. CONCLUSION: These data suggest that acupuncture is an effective and safe adjunctive therapy to conventional care for patients with OA of the knee.

Acupuncture Analgesia↗

Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy.

This prospective, multicenter, double-masked, placebo-controlled study evaluated the safety and efficacy of brinzolamide 1% ophthalmic suspension (Azopt) when used adjunctively with open-label timolol maleate 0.5% (Timoptic). One-hundred-thirty-two patients requiring an adjunctive therapy to timolol 0.5% for the treatment of open-angle glaucoma or ocular hypertension were randomized to receive brinzolamide or placebo three times daily (t.i.d.) in addition to timolol 0.5% twice daily (b.i.d.) for 3 months. Qualifying intraocular pressure (IOP) on timolol 0.5% b.i.d. was 24-36 mm Hg in at least one eye at 8:00 A.M. and 21-36 mm Hg at 10:00 A.M., with no greater than a 5-mm Hg difference between eyes, during two eligibility visits separated by at least 7 days. Treatments were compared using a repeated-measures analysis of variance. Adjunctive therapy with brinzolamide resulted in clinically and statistically significant reductions in IOP from the timolol baseline at all visits. IOP changes from a diurnal baseline ranged from -3.3 mm Hg to -4.1 mm Hg for brinzolamide (N = 53) compared with -0.9 mm Hg to -2.5 mm Hg for placebo (N = 55). Abnormal taste (7.7%) and transient blurred vision (6.2%) were the most frequently reported adverse events. No clinically significant differences in the incidence or severity of ocular signs, visual acuity, cup/disk ratio, or parameters studied on dilated fundus examination were observed between treatment groups. Brinzolamide 1% t.i.d., used adjunctively with timolol 0.5% b.i.d., is safe and well tolerated, and produces clinically and statistically significant additional IOP reductions.

Adrenergic beta-Antagonists↗

Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in developing countries.

OBJECTIVE: To analyse the incremental costs, effects and cost-effectiveness of zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea, including dysentery, and to reassess the cost-effectiveness of standard case management with oral rehydration salt (ORS). METHODS: A decision tree was used to model expected clinical outcomes and expected costs under four alternative treatment strategies. The best available epidemiological, clinical and economic evidence was used in the calculations, and the United Republic of Tanzania was the reference setting. Probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single parameters were explored in one-way sensitivity analyses. FINDINGS: ORS was found to be less cost-effective than previously thought. The use of zinc as adjunct therapy significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness. The results were particularly sensitive to mortality rates in non-dysenteric diarrhoea, but the alternative interventions can be defined as highly cost-effective even in pessimistic scenarios. CONCLUSION: There is sufficient evidence to recommend the inclusion of zinc into standard case management of both dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings from the United Republic of Tanzania to other settings is not justified, but there are no indications of large geographical differences in the efficacy of zinc. It is therefore plausible that our findings are also applicable to other developing countries.

Acute Disease↗

Corticosteroids as adjunctive therapy in bacterial meningitis. A meta-analysis of clinical trials.

A meta-analysis of all nine available controlled trials of corticosteroids for adjunctive therapy for bacterial meningitis was performed. Risks of various outcomes were assessed for control and treatment groups from each study, and risk differences were determined. For each outcome a weighted average of the individual risk differences was calculated. The results show that corticosteroid administration did not reduce the risk of death or neurologic abnormality at hospital discharge or follow-up examination. Based on statistically combined results of the three most recent trials, there is evidence that dexamethasone reduces the risk of bilateral moderate or more severe hearing loss (risk difference, -9%; 95% confidence limits, -15% and -3%). However, this may be true only for children with meningitis caused by Haemophilus influenzae type b. There are inadequate data in adults or in children with meningitis due to other organisms to demonstrate the benefit of dexamethasone administration. Further study is necessary to fully assess the benefits and risks of corticosteroids for adjunctive therapy for bacterial meningitis.

Adrenal Cortex Hormones↗

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Adolescent↗

Adjunctive therapies in the treatment of acute coronary syndromes.

Survival after myocardial infarction has been improving steadily in recent decades, in part because of more effective adjunctive medical therapies. However, the issue of underutilization of effective medical therapies remains. Adjunctive therapy for acute myocardial infarction should include aspirin, beta-adrenergic blocking agents, angiotensin-converting enzyme inhibitors, and lipid-lowering agents, all of which improve survival in the treatment and secondary prevention of myocardial infarction. This review presents the current knowledge supporting the use of specific adjunctive pharmacologic agents and also discusses the current status of other agents that are emerging or controversial.

Acute Disease↗

Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings.

Role of micronutrients namely vitamin A, zinc and folate, as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy. Apart from a selective review, attempts have been made to statistically combine results of several studies to address policy issues. In children, vitamin A supplementation during illness has (a) a profound effect in reducing mortality in measles, (b) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea, and (c) no benefit in pneumonia. Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia. Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture. Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly, bulging fontanelle observed in infants when co-administered at immunization. In children, zinc supplementation during illness, (a) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea, (b) resulted in reduced rate of treatment failure and death in persistent diarrhea, (c) had no effect in measles and non-measles pneumonia, and (d) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children. The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further. Concerning policy, zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea. However, recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness, cost, operations and safety. In two randomized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect. Folate is not recommended as adjunct therapy of diarrhea. Role of folate in preventing severe disease and/or death deserves further evaluation.

Acute Disease↗

Reperfusion adjunctive therapy.

The beneficial effects of coronary thrombolytic therapy may be enhanced by certain adjunctive therapies. Some of these are of proven value, some appear to offer no benefit in spite of theoretical advantages, and some remain to be evaluated in clinical trials. Acetylsalicylic acid markedly enhances the mortality reduction of thrombolytic therapy and should be used routinely. There is a strong theoretical rationale for the use of heparin, but evidence for its benefit exists primarily in small angiographic trials, and convincing clinical benefit has not yet been demonstrated. Early intravenous beta-blockers were shown in the prethrombolysis era to confer modest benefit, but extensive data on their adjuvant use with thrombolysis are available from only one trial. Intravenous nitrates were demonstrated to reduce mortality in the prethrombolysis era, and are soon to be evaluated in trials employing thrombolytic therapy. The calcium channel blockers, in spite of a variety of theoretical benefits, have proved to be of no value acutely, and in the subacute setting, only diltiazem appears to confer benefit in the subgroup of patients with non-O-wave infarction. Angiotensin-converting enzyme inhibitors are likely to be of value in survivors of acute myocardial infarction with left ventricular dysfunction, and benefits observed with acute use in experimental infarction are now being evaluated in clinical trials.

Drug Therapy, Combination↗

The use of dorzolamide and pilocarpine as adjunctive therapy to timolol in patients with elevated intraocular pressure. The Dorzolamide Additivity Study Group.

PURPOSE: To report the results of two studies on the use of dorzolamide as adjunctive therapy to timolol in patients with elevated intraocular pressure (IOP). In the larger study, the additive effect of dorzolamide administered twice daily also was compared with 2% pilocarpine. METHODS: Both studies were parallel, randomized, double-masked, placebo-controlled comparisons. In the pilot study, 32 patients received 0.5% timolol twice daily plus either 2% dorzolamide twice daily or placebo twice daily for 8 days. In the Pilocarpine Comparison Study, 261 patients received 0.5% timolol twice daily plus 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, 2% pilocarpine four times daily, or placebo (twice daily or 4 times daily) for 2 weeks. Patients then entered a 6-month extension period and received 0.5% timolol twice daily plus either 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, or 2% pilocarpine four times daily. RESULTS: In the pilot study, after 8 days, additional mean percent reductions in IOP for 2% dorzolamide and placebo were 17% and 3% at morning trough and 19% and 2% at peak, respectively. In the Pilocarpine Comparison Study, after 6 months, additional mean percent reductions in IOP (morning trough) were 9%, 13%, and 10% for 0.7% dorzolamide, 2% dorzolamide, and 2% pilocarpine, respectively. Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors. CONCLUSION: Dorzolamide twice daily was effective and well tolerated by the patients in these studies as adjunctive therapy to timolol. The larger study demonstrated that both concentrations of dorzolamide produce similar IOP-lowering effects to 2% pilocarpine.

Adrenergic beta-Antagonists↗

Clinical evaluation of subgingival application of metronidazole 25%, and adjunctive therapy.

The effect of topical application of a metronidazole gel (ELYZOL DENTAL GEL), and adjunctive therapy in the treatment of adult periodontitis was assessed clinically. A single, masked examiner performed clinical assessments. Fourteen patients were involved, each one received four different treatments including control, and the four treatments were randomly applied to at least one tooth in each quadrant for each patient in a comparative split-mouth design. Clinical examinations were carried out before treatment and 90 days after treatment. All patients had at least one tooth in each quadrant with probing pocket depth of > or = 5mm. The four treatment groups were: (I) One session of one hour of scaling and root planning, (II) metronidazole 25% dental gel (ELYZOL DENTAL GEL) applied on day 0 and day 7, (III) scaling adjunctive to metronidazole 25%, and (IV) No treatment. Instruction in oral hygiene was given to all subjects at base line examination. At the end of the study (day 90), all groups had statistically significant improvement in probing pocket depth (P < 0.02), and in plaque and bleeding indices (P < 0.05) when compared to day 0. However, group III had statistically significantly greater improvement (P < 0.03) in probing pocket depth than groups I, II and IV. Both groups I and II had statistically significantly greater improvement (P < 0.05) in probing pocket depth than control group. On the other hand, both groups were not statistically significantly different from each other in probing pocket depth improvement. It is suggested that topical Elyzol treatment may improve periodontal health as well as subgingival scaling and root planning therapy, and adjunctive treatment could obtain an additional therapeutic effect.

Administration, Topical↗

Hemodialysis as adjunctive therapy for severe acetaminophen poisoning: a case report.

Acetaminophen overdose is a common intoxication in daily practice the standard treatment is N-acetylcysteine (NAC) antidotal therapy for possible poisoning. However, dialysis procedures can remove the drug from the body effectively. We describe a case of acetaminophen overdose that was treated with both hemodialysis (HD) and NAC due to severe intoxication and slow drug clearance. A 37-year-old woman attempted suicide by ingestion of 100 tablets (500 mg each) of acetaminophen, and presented with vomiting, hematemesis and abdominal pain. The patient had elevated liver enzymes, coagulation defects, thrombocytopenia a high serum acetaminophen level (201 mg/l at 12 hours post-ingestion) with a prolonged half-life. Oral NAC was given; however, it was ineffective due to severe vomiting and hematemesis. HD as adjunctive therapy was initiated at 19 hours post-ingestion. HD reduced the serum acetaminophen level from 102.77 to 35.77 mg/l. Severe hepatic injury, bacteremia and pancytopenia were noted in the following days. The patient later recovered after treatment with NAC, HD and intensive supportive care. HD removed 66% of the total acetaminophen body burden during a single four-hour session, increased the clearance by 2.75-fold and shortened the half-life from 7.2 hours to 2.6 hours during HD. Through NAC therapy is the standard regimen for acetaminophen poisoning, in the severely poisoned patient who cannot tolerate NAC therapy, HD may be used as adjunctive therapy to enhance the elimination of acetaminophen.

Acetaminophen↗

Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone.

PURPOSE: We compare the efficacy of testosterone gel (T-gel) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. MATERIALS AND METHODS: A randomized, placebo controlled, double-blind, parallel group, multicenter study was performed. A total of 75 hypogonadal men (18 to 80 years old, morning serum total testosterone 400 ng/dl or less) with confirmed lack of response to sildenafil monotherapy were randomized (1:1) to receive a daily dose of 1% T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period. Subjects were evaluated for sexual function, primarily based on the International Index of Erectile Function (IIEF), quality of life and serum testosterone levels at baseline and weeks 4, 8 and 12. RESULTS: Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo, reaching statistical significance at week 4 (4.4 vs 2.1, p = 0.029, 95.1% CI 0.3, 4.7). Similar trends were observed for improvements in orgasmic function, overall satisfaction, total IIEF score and percentage of IIEF responders. T-gel significantly (p < or =0.004) increased total and free testosterone levels throughout the study, although no significant correlations were made between testosterone levels and the IIEF at end point. CONCLUSIONS: T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone.

Adolescent↗

Antioxidant vitamins E and C as adjunct therapy of severe acute lower-respiratory infection in infants and young children: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of antioxidant Vitamins E and C as adjunct therapy of severe acute lower respiratory infection (ALRI) in children. DESIGN: Randomized double-blind placebo-controlled clinical trial. SETTING: A large childrens' hospital serving the urban poor in Kolkata, India. SUBJECTS: Children aged 2-35 months admitted with severe ALRI. INTERVENTION: In total, 174 children were randomly assigned to receive alpha-tocopherol 200 mg and ascorbic acid 100 mg twice daily or placebo for 5 days. All children received standard treatment for severe ALRI. Outcome measures were: time taken to recover from a very ill status, fever, tachypnoea, and feeding difficulty; and improvement in oxidative stress and immune response indicated by thiobarbituric acid reacting substances (TBARS) and response to skin antigens, respectively. RESULTS: Recovery rate ratios (95% CI) using proportional hazards model were 0.89 (0.64-1.25), 1.01 (0.72-1.41), 0.86 (0.57-1.29), and 1.12 (0.77-1.64) for very ill status, feeding difficulty, fever, and tachypnoea, respectively. TBARS values were high and similar in the two groups at admission, discharge, and at 2 weeks follow-up. Serum alpha-tocopherol significantly increased in treated group at discharge. Immune response to skin antigens were very poor at admission and after 2 weeks, in both groups. CONCLUSION: Infants with severe ALRI failed to benefit from two antioxidant nutrients as adjunct therapy. Severe ALRI in infants may cause cell-mediated immune dysfunction. We need a better understanding of oxidative processes in growing infants to help us better design interventions with antioxidant therapy.

Acute Disease↗

Adjunctive therapies in nutritional support.

The need for new therapeutic approaches to improve the metabolic and clinical efficacy of nutritional therapy has been increasingly emphasized. The field of nutrition support of catabolic, malnourished, or hospitalized patients is rapidly evolving in response to the beneficial effects observed with adjunctive therapies in animal models and in emerging clinical investigations. Enteral nutrition is being increasingly administered, and enteral diets are being tested to improve gut structure and function. Adjunctive therapies in enteral and parenteral nutrition are being actively investigated. These include administration of recombinant growth factors and anabolic steroid hormones (e.g., growth hormone, oxandrolone); conditionally essential amino acids (e.g., arginine, glutamine); novel lipid products (e.g., structured lipids, fish oils); nutrient antioxidants (e.g., vitamins C and E); and combinations of these approaches. It is likely that current methods of enteral and parenteral nutrition support will evolve in response to the results of these research studies.

Amino Acids, Essential↗