Course Of Oral Therapy Research Articles

Abstract P5-15-07: Let's talk about it: Communicating about risk of recurrence in early-stage breast cancer

Abstract Introduction: Risk of recurrence underlies virtually all decision-making in early-stage breast cancer (EBC). Yet, patients and physicians (HCPs) express challenges, limitations, and unmet needs related to HCP-patient communication about recurrence risk. Methods: This qualitative study included: (A) 16 individual interviews with patients diagnosed with EBC in the last 2 years, for their ability to draw on their experience and (B) 2 focus groups with consumers who have never had a cancer diagnosis, for their ability to provide the “cancer-naïve” perspective that may more closely match newly diagnosed patients. Prior to and after the qualitative research, several breast cancer HCP thought leaders were consulted regarding questions and takeaways. Patients were identified via Wellness House, a cancer support organization, whose staff provided counseling support in case the topic was distressing to interviewees. Consumers were identified via a nationwide market research panel. Research took place online in 02/2021. Within the domain of HCP-patient communication about risk of recurrence, questions differed a bit for patients vs consumers but focused on: Experience, Desires, Objectives, and Reactions to methods of explaining risk. Discussion guides, recruiting/screening materials, informed consent documents, and processes were submitted to Advarra IRB and received exempt status. Results: A total of 32 women (16 patients; 16 consumers) participated, with a mix of ages, educational attainment, and racial and ethnic social identities. Information needs were high with objectives centered on being part of treatment decision-making and being motivated to adhere to treatment, screening, and follow-up. Respondents noted that communication about hard topics is central to building a trusting HCP relationship. Many patients felt they had not heard much about their risk, with some admitting they did not want to hear about it. HCPs face a mix of attitudes, but no patients thought they were told too much. Communication timing was a central theme. Many described the information overload that occurs at/near diagnosis and felt they might need a general understanding of recurrence risk at that time, with intentional revisiting of recurrence risk at each decision or transition point (most often connected to changes in modalities or treatments). Within ER+/HER2- disease, patients discussed the transition to oral (endocrine) therapies and specifically noted that time with physicians was limited at that point. In such cases, recurrence risk was insufficiently linked to the recommendation to take a long course of oral therapy that often has significant side effects. Some interviewees were reticent to continue oral therapy, particularly without knowing why it mattered. Communication methods garnered a wide mix of reactions and revealed misinterpretations, underscoring the need to simplify and individually tailor tools. Some group-level tailoring is also possible with degree of risk over time differing by subtype and stage. From a “misunderstanding” standpoint, it seemed time horizons were even less likely to be recalled or understood by patients with ER+/HER2- disease. Respondents focused on wanting information on how they could reduce risk (e.g., diet, exercise, alcohol) and many felt they received inadequate information from HCPs. This led them to search elsewhere for such information. Conclusions: Improving HCP-patient communication about risk of recurrence appears very likely to contribute to shared decision-making and adherence. In particular, the timing of communication may offer a key opportunity to achieve these objectives. In addition, providing tips and tools to oncologists to enhance two-way communication may be helpful, particularly to simplify and tailor by subtype and patient need. Citation Format: Mary L Smith, Elda M Railey, Carol B White. Let's talk about it: Communicating about risk of recurrence in early-stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-15-07.

Chronic hepatitis B: early viral suppression and long‐term outcomes of therapy with oral nucleos(t)ides

Chronic hepatitis B is a serious health problem worldwide with a substantial minority of patients experiencing premature death due to end-stage liver disease and/or hepatocellular carcinoma. Antiviral therapy may help prevent complications of chronic hepatitis B, and seven agents are currently approved in many countries. Of these agents, five are nucleos(t)ide analogs that all have a risk of antiviral drug resistance with long-term use. Efforts have been made in the recent years to prevent or to reduce the risk of viral resistance in patients treated with oral nucleos(t)ides as the majority of these patients will require therapy for 3-5 years or longer. One approach is to identify patients who would most likely develop antiviral resistance on long-term therapy using predictors obtainable early in the course of treatment, when intervention with new or additional therapy can be instituted. The most important predictors of treatment outcomes are serum HBV DNA levels at baseline and during the first 6 months of therapy. The purpose of this synopsis is to review the recent literature regarding the importance of serum HBV DNA levels in association with treatment outcomes in chronic hepatitis B, particularly the association of complete viral suppression early in the course of oral therapy with long-term treatment outcomes, particularly the incidence of antiviral drug resistance.

Chronic Invasive Fungal Rhinosinusitis: Two New Cases and Review of the Literature

Chronic invasive fungal rhinosinusitis is rare in the immunocompetent patient. Few cases have been published except for in a specific geographic area (Sudan, India). We reported two new cases of chronic invasive fungal rhinosinusitis due to Aspergillus, which was successfully treated, to analyze the different clinical, radiological, and mycological criteria. Through these two new clinical cases and the analysis of the literature, we suggested, in the absence of general agreement on the surgical and medical management, the current strategies available for this rare pathology. New antifungal drugs seem to be an efficient alternative to classic antifungal agents, especially those that require an extended course of oral therapy for the chronic invasive form.

An Ex-Vivo Pharmacodynamic Study Comparing Bactericidal Activity of Amoxicillin/Sulbactam, Azithromycin, Doxycycline and Levofloxacin Against Streptococcus pneumoniae

We designed a 4-way crossover, Ex-Vivo pharmacodynamic study to compare the bactericidal rate of amoxicillin/sulbactam (AMX-SUL), azithromycin (AZM), doxycycline (DOX) and levofloxacin (LVX) against Streptococcus pneumoniae ATCC 49619. Six volunteers were randomized to receive alternatively a single tablet of the above drugs. Venous blood samples were obtained immediately before and at 2, 4 and 6 h after dose to perform time-kill studies and to determine antibiotic levels in serum. AMX-SUL was the only drug showing bactericidal activity with the sera obtained at every time after dose, as defined by a ≥ 3-log10 cfu/ml decrease in the viable cell counts compared to the original inoculum after a 24-h incubation. AZM was only inhibitory at 2h after dose (i.e. a 1.3-log10 cfu/ml decrease in the viable cell counts) and proved bactericidal at 4 and 6 h post-dose. LVX proved bactericidal with the 2-h serum, was only inhibitory with the 4-h serum (e.g. a 1.5- log10 cfu/ml decrease) and was unable to avoid bacterial growth at 6 h post-dose. Bacterial growth was observed with DOX at every time after dose. This study may shed light on the understanding of breakthrough pneumococcal bacteremia during the course of oral therapy with AZM in patients with community-acquired pneumonia (CAP), as well as the increasing treatment failures observed with LVX, and the selection of bacterial resistance during therapy reported with both drugs. It also provides the basis for a “warning signal” on the use of oral DOX and confirms the efficacy of AMX-SUL.

An open-label, multicenter study of the combination of amorolfine nail lacquer and oral itraconazole compared with oral itraconazole alone in the treatment of severe toenail onychomycosis

Background: Data indicate that combination therapy may provide enhanced clinical and economic benefits over monotherapy in the treatment of onychomycosis. Objective: The aim of this study was to compare the efficacy of 2 topical amorolfine/oral itraconazole combination regimens with oral itraconazole alone in the treatment of severe toenail onychomycosis. Cost implications of all treatments were assessed in a pilot pharmacoeconomic analysis. Methods: In this multicenter, open-label, 24-week study, patients were randomized to 3 parallel treatment groups: 5% solution of amorolfine nail lacquer applied once weekly for 24 weeks plus itraconazole 200 mg once daily for either 6 weeks (group AI-6) or 12 weeks (group AI-12), or itraconazole alone for 12 weeks (group I-12). Results: Mycologic cure at week 12 was achieved in 93% of patients in group AI-6, 83% in group AI-12, and 41% in group I-12. Combination therapies were significantly more effective than itraconazole monotherapy ( P < 0.001). Global assessment (combined measure of mycologic and clinical cure rates) at 24 weeks demonstrated cure rates of 84% for patients in group AI-6, 94% in group AI-12, and 69% in group I-12. The difference between the AI-12 group and the I-12 group was statistically significant ( P < 0.05). There were no serious adverse events during the study, and the distribution of adverse events was not significantly different between groups. Pharmacoeconomic assessment demonstrated that both durations of combination therapy were more cost-effective than monotherapy. Conclusions: Our results show that topical amorolfine combined with oral itraconazole was more effective in treating severe toenail onychomycosis than was itraconazole monotherapy. Combination with a short course of oral therapy had a marked pharmacoeconomic advantage over the other regimen, suggesting that switching from the current 12-week itraconazole monotherapy to the 6-week combination therapy would cure more patients for a lower cost.

Septic Arthritis Caused by Burkholderia Pseudomallei: Case Report and Review of the Literature

We describe a case of septic arthritis and bacteremia caused by Burkholderia pseudomallei, a bacterium that is endemic in East Asia and northern Australia. We believe that dissemination occurred in our patient after surgical excision of a pulmonary nodule. Bacteremic melioidosis can present with musculoskeletal involvement in 2-10% of patients, but septic arthritis is uncommon. A review of the literature shows a total of 66 patients reported with septic arthritis caused by this organism. Patients with septic arthritis caused by Burkholderia pseudomallei were likely to have diabetes mellitus, and the knee is the joint most frequently affected by this organism. Recommended initial treatment consists of ceftazidime, alone or in combination with trimethoprim/sulfamethoxazole, high dose imipenem/cilastatin, or high dose cefoperazone/sulbactam. This is followed by a 12-20 week course of oral therapy (based on susceptibilities) to eradicate the organism. Most patients with subacute or latent disease do well after full antibiotic treatment, but relapses are common if full treatment is not given. Awareness of this disease is important even in areas outside of Asia given the increasing frequency of international travel and the growing likelihood of imported cases, along with an aging population of Vietnam veterans and immigrants.

Outpatient parenteral antibiotic therapy. Managemnt of serious infections. Part II: Amenable infections and models for delivery. Emergency department and urgent care center.

Two approaches to outpatient parenteral antibiotic therapy are commonly used in the emergency care setting. One is daily administration of a parenteral antibiotic followed by oral therapy if clinical response has been satisfactory. The other is administration of a single parenteral dose to initiate a course of oral therapy. Both treatment strategies have proved effective in preliminary studies.

Short and Long Courses of Ofloxacin Therapy of Klebsiella pneumoniae Sepsis Following Irradiation

Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The optimal length of therapy of such infection is not established. The effect of short and long courses of oral therapy with the quinolone ofloxacin for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy of bilateral radiation from 60Co. A dose of 10(8) organisms was given orally 4 days after irradiation, and therapy was started 1 day later. Cultures of the ileum 7 days after irradiation showed the recovery of K. pneumoniae in 7 of 10 untreated mice and in 3 of 20 treated with ofloxacin. However, 14 days after irradiation K. pneumoniae was isolated in 5 of 6 untreated mice, in 7 of 9 that received the short course of therapy, and in one of those that received the long course of therapy (P less than 0.05). At Day 7, K. pneumoniae was isolated from the livers of 6 of 10 untreated mice, and from none of those receiving ofloxacin (P less than 0.05). At 14 days, K. pneumoniae was isolated in 4 of 6 untreated animals, in 4 of 9 that received the short course of therapy, and in none of the mice that received the long course of therapy (P less than 0.05). Only 3 of 20 (15%) untreated mice survived for 30 days as compared to 11 of 20 (55%) mice treated for 7 days with ofloxacin and 18 of 20 (90%) mice treated for 21 days with ofloxacin (P less than 0.05). These survival data illustrate the efficacy of a 21-day course over a 7-day course of ofloxacin therapy for orally acquired K. pneumoniae infection in irradiated hosts.

Evolution of a strategy for the treatment of acne

The management of skin disease may differ in different parts of the world, but in most countries, acne should be a most treatable disease. Acne therapy has not evolved in the most logical fashion, but this article reviews our demonstration of risk factors in the treatment of acne. Young patients, male patients, truncal acne, a marked seborrhea, and a low dose (500 mg/day or less) of tetracycline are factors associated with a poorer response and, when oral therapy is stopped, a greater relapse rate. One gram a day of tetracycline, given for 6 months, is the minimum course of oral therapy and should be given along with topical therapy. One of the most widely used topical treatments is benzoyl peroxide, and this presentation was given in honor of Dr. William Pace, who was possibly the first dermatologist to be aware of the benefit of benzoyl peroxide--a fact not adequately recorded in dermatologic history. A small number of patients do not respond well to conventional therapy, but alternative treatments should bring about a successful outcome. Alternative treatments include hormonal therapy (i.e., 2 mg cyproterone acetate plus 50 micrograms ethinyl estradiol; spironolactone, 100 mg twice daily; or isotretinoin, 1 mg/kg). The success of all these treatments bears some relationship to their effect in modulating the etiologic factors of acne: an enhanced sebum production, increased ductal cornification, abnormal bacterial colonization, and the production of inflammation. Isotretinoin is the most beneficial of all drug regimens, and this fact no doubt relates to its favorable effect on all etiologic factors.

A double-blind study comparing ritodrine and terbutaline in the treatment of preterm labor

One hundred women in preterm labor were randomly treated with ritodrine or terbutaline in a double-blind fashion. The drugs were comparably effective during intravenous therapy but, in women with intact membranes, an oral dose of terbutaline, 30 mg daily, was significantly more effective than ritodrine, 120 mg daily, in preventing recurrent labor during a 5-day course of oral therapy (one of 19 versus 12 of 23, p less than 0.001). In women with intact membranes, pregnancy was prolonged 40 +/- 25 days (mean +/- SD) in women receiving terbutaline orally and only 22 +/- 24 days in women receiving ritodrine orally (p less than 0.01). In women with intact membranes, a heart rate greater than or equal to 130 bpm occurred in in a higher proportion of women receiving intravenous treatment with ritodrine than among those receiving terbutaline (20 of 31 versus 8 of 27, p less than 0.05). Terbutaline-treated women, however, were significantly more likely to have a serum glucose level in excess of 140 mg/dl than were women treated with ritodrine (13 of 26 versus 6 of 29, p less than 0.05). Side effects commonly observed during intravenous therapy included nausea (22%), chest pain (15%), and shortness of breath (15%). Side effects were significantly (p less than 0.025) more likely to occur during periods when the infusion rate was being increased rather than during periods when the infusion rate was constant.

Effects of Keto Analogues of Essential Amino Acids in Portal-Systemic Encephalopathy

Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.

Treatment of acne vulgaris. Use of systemic antibiotics and sulfonamides.

The authors have studied the effectiveness of selected orally administered antibiotics and sulfonamides in treating certain moderately severe to very severe forms of acne. All patients had failed to respond satisfactorily to other measures. However, the systemic antibacterial agents were used as supplementary, rather than substitute, methods of therapy. Evaluation is made of the nature and degree of side-effects of long-term and short-term use of these drugs. There were 312 courses of oral therapy administered from 2 days to 6 years 9 months to 208 patients. The results were excellent in 13 of the courses, good in 196, fair in 86 and poor in 17. Side-effects included Candida albicans vaginitis (the only severe complication requiring therapy), diarrhea, mild nausea, and changes of total or differential white blood cell count. Only 27 patients had complaints which necessitated the discontinuation of the drug used.

Experiences in one hundred thirty-seven patients treated with oral griseofulvin. Special reference to clinical recurrences. the healthy carrier state, and their management.

Shortly after the original publication of Gentles 1 on the effectiveness of griseofulvin in Trichophyton infections of laboratory animals, numerous investigators have reported on striking clinical results obtained with the oral administration of griseofulvin in treatment of superficial dermatomycoses in man. Williams et al., 2 Riehl, 3 Blank and Roth, 4 and Pardo-Castello 5 were among the first attempting such clinical studies. A main purpose of this paper is to evalu ate the recurrences noted in patients either after completion of a course of oral therapy with griseofulvin or in evidence during the course of treatment . The management of these cases will be discussed. Several patients, moreover, were found to have persistently positive mycological laboratory findings despite apparent clinical cure. This situation we have designated as the healthy carrier state. Method We wish to call attention to the fact that our studies commenced in the winter months and extended into

Clinical Manifestations and Treatment of Epidemic Amebiasis Occurring in Occupants of the Mantetsu Apartment Building, Tokyo, Japan 1

Summary 1. The clinical manifestations and treatment of one hundred cases of amebiasis occurring among American occupants of an apartment building in Tokyo, December 1946 to June 1947, are presented. 2. The relative mildness of the clinical manifestations was possibly related to the fact that the period of probable exposure to infection with E. histolytica had been brief; also the epidemic had been recognized soon after the onset of symptoms. There were no fatalities. 3. Seventy-six of the patients were treated with carbarsone and diodoquin; the remainder were given emetine hydrochloride concurrently with carbarsone. 4. Of the total number of patients treated three continued to pass cysts of E. histolytica after one course of treatment; two of these had negative stools after a second course of treatment; one patient, a child, required four courses of oral therapy of varying dosages before the stools were found to be negative. Seventeen continue to have occasional episodes of mild diarrhea and/or abdominal cramping, despite repeated post treatment negative stools.