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Pharmacokinetics in drug therapy. I: Propranolol hydrochloride as adjunct therapy in the treatment of thyrotoxicosis.

A case study in which propranolol hydrochloride was used as adjunct therapy in the treatment of atrial fibrillation with rapid ventricular response, thyrotoxicosis and high output heart failure is presented to illustrate the pharmacokinetics of this drug. The relationship of propranolol dosage to blood levels, the effect of blood levels on pharmacological response, the metabolism and elimination of propranolol, and determination of rational dosage of the drug, are discussed.

Antithyroid Agents

The logic of adjunctive therapy in surgical patients with resectable cancer.

The principles and rationale of using multiple modalities (surgery, chemotherapy, radiotherapy, and immunotherapy) to treat solid malignancies is reviewed. Animal models of human tumors have clearly demonstrated the superiority of combining local treatment (eg, surgery) with systemic treatment (eg, chemotherapy). Although the results of many trials of adjunctive therapy in man are still preliminary, they warrant the caustious generalization that multiple modality therapy will increasingly become more effective than surgery alone for most types of solid tumors. Although the strategy of employing adjunctive therapy is rational, it must be emphasized that the therapeutic efficacy of specific drugs or agents for particular patients or tumor types has not always been satisfactory. Clinical trials now in progress may demonstrate more effective regimens. In the meantime, physicians should be cautious about using adjunctive therapy as standard treatment until long-term benefits and safety have been demonstrated. Participation in clinical trials is encouraged to verify the validity and application of this therapeutic approach.

Animals

Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans

Primary carcinoma of the gallbladder. The role of adjunctive therapy in its treatment.

Of forty-three patients with carcinoma of the gallbladder discovered ih a twenty-five year period (during which 10,349 patients were diagnosed as having cholelithiasis), eighteen patients (42 per cent) had no obvious tumor outside of the gallbladder at the time of operation, nineteen patients (44 per cent) had local spread of the disease, and six patients (14 per cent) had abdominal carcinomatosis or distant metastasis. In the twenty-one patients who underwent surgical therapy for cure of their disease, the five year survival rate was 33 per cent. The more extensive surgical procedures (other than cholecystectomy alone) did not significantly increase survival. Neither the duration of the symptoms nor the pathologic type of the tumor altered the eventual outcome. No patients with tumor outside the gallbladder at the time of operation survived longer than two years. Compared to those who did not receive it, the fifteen patients treated postoperatively with adjunctive therapy (radiation therapy or chemotherapy or both) lived longer and also were significantly better palliated when tumor outside of the gallbladder was found at the time of operation. From these findings, the routine use of adjunctive therapy is recommended in all patients with disease outside of the gallbladder and serious consideration should be given to its use in all patients found to have carcinoma of the gallbladder.

Adenocarcinoma

Fresh-frozen plasma vs. plasma protein derivative as adjunctive therapy for patients with massive burns.

Twenty patients with burn injuries involving 45% or more total body surface area were randomly allocated to receive either fresh-frozen plasma (plasma), 200 ml/m2/d (11 patients), or an approximately equal amount of plasma protein derivative (Plasmanate) (nine patients) during the first 45 days postburn. To study the potential effects of these two adjunctive therapies on host resistance to infection, measurements were made twice weekly of the antibacterial funciton of neutrophils, the opsonic index (ability to opsonize alternative pathway dependent E. coli 075), C3(B), IgG, properdin, factor B, total protein, and albumin. The average size of burn in the plasma group was 61.5% total and 42% 3 degrees compared with 61% total and 46% 3 degrees in the Plasmanate group. Ten and 18 episodes of bacteremia occurred in the plasma and Plasmanate groups, respectively. Analysis of the results indicates only slightly better support of host resistance when plasma is administered, but this is counterbalanced by the increased risk of viral hepatitis.

Adolescent

Recent progress in chemotherapy and immunotherapy of sarcomas of bony origin, both as primary and adjunctive therapy.

Treatment for primary malignant tumors of bone, in the past several decades, has yielded uniformly poor results. Recent progress in chemotherapy and immunotherapy are detailed. An important advance in treating osteogenic sarcoma has been the application of adjuvant chemotherapy after initial amputation. CONPADRI-I and COMPADRI-II chemotherapy (a multiple drug approach) is discussed. Adriamycin in combination or alone has proved effective in treating osteogenic sarcoma. Ewing's tumor is showing increased survival rates from radiation therapy alone, as well as by use of systemic adjuvant chemotherapy combined with local radiation. Adjuvant triple chemotherapy with radiotherapy has resulted in pronounced improvement in survival. Chondrosarcomas are largely chemotherapy-resistant. Immunotherapy in bone tumors still is in the experimental stage and investigations with immunotherapy are preliminary. It appears, however, that the immunological status of a patient definitely relates to prognosis. Through increased sophistication in specific chemotherapy and magnitude of treatment, further advances in treatment of primary malignant bone tumors may be expected.

Amputation, Surgical

Retroperitoneal lymphadenectomy as adjunctive therapy in selected cases of advanced testicular carcinoma.

The findings in 10 patients with advanced non-seminomatous testicular malignant disease in whom either complete remission or reduction in clinical stage was achieved with chemotherapy and later retroperitoneal lymphadenectomy are presented. The procedure in these selected instances allowed for a more accurate assessment of the disease status. The operative findings served as an accurate guide to determine the need for further drug therapy.

Adolescent

Adjunctive therapy in treatment for head and neck cancer.

Improvement in tumor-free intervals and cure rates of patients with cancer of the head and neck will almost certainly come from utilization of more than one type of treatment in the same patient. For example, in treatment for formidable lesions this might take the form of a short course of preoperative chemotherapy followed by surgery. Postoperative chemotherapy might then be employed in preoperative responders, with the addition of radiation according to the usual postoperative indications. Specific or nonspecific immunotherapy might be used on a long-term basis, preoperatively and postoperatively. In selected patients, utilization of multiple modalities early in a careful long-term plan may bring improvement over current results from employment of adjuvant measures only after recurrence or metastatic spread is clinically obvious.

Antineoplastic Agents

Corticosteroids as adjunctive therapy for acute bacterial meningitis.

Although anecdotal reports and the results of clinical trials suggest that corticosteroids may be efficacious in the treatment of acute bacterial meningitis, controlled and double-blind studies fail to support this view with the exception that corticosteroids may be of benefit for patients with pneumococcal meningitis. Corticosteroids may also be of benefit to patients with acute bacterial meningitis in the presence of life-threatening complications of increased intracranial pressure, such as coma, seizures, fluctuating blood pressure, or rapidly deteriorating mental status, but results of controlled or double-blind studies to substantiate this have not been reported. The possible advantages gained from the use of corticosteroids must be considered with regard to a significant detrimental effect in patients over 16 years of age.

Acute Disease

Therapeutic evaluation of Elase as adjunctive therapy in the treatment of monilial vaginitis.

The effectiveness of a lytic enzyme preparation (Elase--Parke-Davis) plus natamycin (Pimafucin--Gist-Brocades) was compared to natamycin therapy alone in a controlled clinical trial involving 120 patients suffering from monilial vulvo-vaginitis. The results indicate that addition of Elase to a natamycin treatment regimen increases the effectiveness of therapy both with respect to alleviation of symptoms and to eradication of the organism as determined by vaginal culture in patients with acute infection and in those in whom infection is complicated by pregnancy or diabetes.

Candida albicans

The efficacy of rifampin as adjunctive therapy in selected cases of staphylococcal endocarditis.

Three patients with bacterial endocarditis (one case due to Staphylococcus aureus and two to S epidermidis) failed to improve on standard therapeutic regimens which were judged adequate by in vitro testing for sensitivity. Rifampin was added to the regimen in each case and resulted in increased bactericidal activity in the serum, sterilization of the cardiac valves, and clinical cure. The apparent clinical success that was achieved suggests that further investigation of the effectiveness of therapy with rifampin in selected cases of staphylococcal endocarditis is warranted.

Adult

Clindamycin vs placebo as adjunctive therapy in moderately severe acne.

Eighty-three patients with moderately severe acne were entered into a double-blind study utilizing clindamycin and placebo. Counts of comedones and pustules were made at intervals during a 13-week period. Clindamycin resulted in noticeable improvement of acne in 85% of subjects while in the placebo group improvement was present in 38%. There was also an unexplained reduction of total comedone count in the clindamycin-treated group. Severe side effects occurred in two of 44 patients receiving clindamycin (diarrhea, 1 and rash, 1); although an additional eight patients receiving clindamycin experienced mild diarrhea, discontinuation of therapy was not required. Clindamycin appears to be a valuable additional drug in the treatment of acne.

Acne Vulgaris

A trial of sulfasalazine as adjunctive therapy in Crohn's disease.

The effect of the combination of sulfasalazine and prednisone has been compared with that of prednisone and placebo in 89 actively symptomatic patients with Crohn's disease in a double-blind, randomized, multicenter controlled trial. The combination was less effective than prednisone alone in treatment of active symptomatic disease. The probability of obtaining this result, if sulfasalazine truly has a clinically useful effect equal to or greater than that specified in the calculation, is less than 1%. Patients who were in remission at the end of 8 wk were rerandomized to receive either the two drugs together or prednisone plus placebo while repeated systematic attempts to withdraw prednisone were made over the next 6 mo. Sulfasalazine showed no prednisone-sparing effect as judged either by outcome ranking or total dose of prednisone consmed by the two treatment groups. However, in this comparison the probability is greater than 5% that, given the results observed, a clinically useful effect of sulfasalazine of specified minimum degree truly exists. It was possible to withdraw prednisone from 25% of patients at the first attempt and ultimately in 37%.

Adult

Periodontal therapy in humans. I. Microbiological and clinical effects of a single course of periodontal scaling and root planing, and of adjunctive tetracycline therapy.

The present results showed that maarked and long-lasting changes in the subgingival microflora associated with periodontal disease could be achieved by a single course of periodontal treatment. Immediately following therapy, the total number of subgingival organisms decreased 10- to 100-fold and the proportions of cultivable Gram negative organisms and anaerobic organisms generally decreased 3- to 4-fold or more. After treatment, most periodontal pockets were populated by a scant microflora predominated by facultative Actinomyces and Streptococcus species. The kinetics of the subgingival bacterial recolonization revealed that the total cell counts and the proportions of spirochetes and Capnocytophaga species did not reach their pretreatment levels even after 6 months. Other Gram negative anaerobic species returned to pretreatment proportions after 3 to 6 months. Several Gram positive species exhibited higher posttreatment than pretreatment proportions throughout the 6 months study. The microbiological shifts paralleled significant changes in the clinical status of the periodontal tissues. Following therapy, the periodontal pocket depths decreased generally 1 to 4 mm, the gingival inflammatory index, the gingival fluid flow, and the suppurative index were generally lower, and nine of 33 test pockets examined showed apposition of alveolar bone. The microbiological and clinical changes described were exhibited by two patients treated with periodontal scaling and root planing alone and by two patients treated with the adjunctive use of systemic tetracycline therapy. In two other patients, mechanical periodontal therapy only slightly reduced the total number of subgingival organisms and the proportions of spirochetes and other Gram negative anaerobic rods. A shift in the subgingival microbial composition was achieved in these two patients after tetracycline therapy. The following model for treatment of periodontal disease is proposed: (1) Conventional therapy including thorough periodontal scaling and root planing; (2) Monitoring the subgingival flora and the clinical course; and (3) Use of antimicrobial therapy in refractory cases. Further studies are needed to develop means for rapid identification of refractory patients, and to determine the optimal antimicrobial agent, the optimal route of administration, and the optimal dosage regime.

Actinomyces