Evaluating Patients' Preferences Regarding Treatment Options for Waldenström's Macroglobulinemia, a Discrete-Choice-Experiment

Introduction The management of Waldenström's Macroglobulinemia (WM), a rare and incurable B-cell non-Hodgkin lymphoma, has evolved in recent years. Treatment options are increasing including more modern targeted therapies. Therefore there are currently several effective treatment options available for WM. There is no consensus on a preferred treatment. Widely used treatment options include rituximab combined with chemotherapy, proteasome inhibitors, and the oral BTK inhibitor ibrutinib. These treatments have varying properties in terms of efficacy, toxicity profile, duration (fixed-duration vs long-term maintenance), administration (oral vs intravenous/subcutaneous (IV/SC)), and type of agent (chemotherapy vs targeted therapy). A better understanding of patients' treatment preferences could aid physicians in developing an individualized treatment plan. Also, a better insight in patients' treatment views could help direct future clinical studies in WM. However, treatment preferences of WM patients have not been investigated. We aimed to evaluate treatment preferences of WM patients by means of a discrete choice experiment (DCE) and to assess the importance of different attributes describing the currently available treatment regimens. Methods A mixed-method approach, consisting of a literature review, qualitative interviews and expert discussions was utilized for identification and selection of attributes/levels. A DCE questionnaire was developed in Dutch and included 5 treatment-related attributes: 5-year progression-free survival (PFS), frequency/route of administration(IV/SC or oral)/setting (clinic or home) of treatment, adverse events (nausea & vomiting and fatigue, neuropathy and atrial fibrillation), risk of future secondary malignancies (low vs high), and type of treatment agent (chemotherapy or targeted therapy). Each respondent was presented with 16 choice cards and was asked to choose between two hypothetical but realistic treatment options (see Figure 1 for an example). A pilot DCE study was carried out in 5 patients to evaluate feasibility. Data were collected via a nationwide online questionnaire via the patient organizations' website and via paper-based questionnaires sent to the participants known at the outpatient clinic. An orthogonal design was used to construct the choice tasks and a mixed logit panel data model was used to assess patients' preferences and trade-offs between attributes/levels. Results A total of 330 online questionnaires and 17 paper-based questionnaires were returned. After excluding incomplete survey data, 214 (65%) questionnaires were included for data analysis, respondents characteristics are presented in Table 1. The 5-year PFS followed by the risk of secondary malignancies were the most important attributes for making treatment decisions. The probability of choosing a treatment option increased with 26% and 22% if the 5-year PFS increased from 50% to 70% and if the chance of future secondary malignancies was decreased from "high risk" to "low risk", respectively. Of the adverse events, patients disliked being at risk for neuropathy the most more than nausea, vomiting and extreme fatigue. Patients were willing to give up 7,2% treatment efficacy to avoid risk of neuropathy. The probability of choosing a treatment option increased with 8% for a fixed-duration treatment with IV/SC administration at the hospital compared to an ongoing daily oral regimen at home (Table 2). Socio-demographic characteristics such as age, gender and treatment status did not significantly influence patients' preferences with the exception of educational status. Lower 5-year PFS was more acceptable for patients with higher education (P<0.0001 ) and this subgroup of patients preferred a treatment with targeted therapy and low risk of secondary malignancy (P<0.0001). Conclusion These are the first data on WM patients' preferences on treatment characteristics. We found that Dutch WM patients find efficacy (high 5-year PFS rate) the most important attribute, followed by a low risk of future secondary malignancies. Neuropathy was the adverse event they most wanted to avoid. They preferred a fixed-duration IV/SC treatment over an ongoing oral regimen. These data can be used in discussions with individual patients about their treatment preference, and help direct future clinical trials that optimally connect to WM patients' preferences. Figure 1 Figure 1. Disclosures Minnema: Cilag: Consultancy; Janssen: Consultancy; Celgene: Other: Travel expenses; Alnylam: Consultancy; BMS: Consultancy; Kite/Gilead: Consultancy. Kersten: Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel support; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Vos: Celgene: Other: Travel reimbursement; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

Background: Owing to dysregulated immune response, secondary bacterial pulmonary infections involving both gram-positive and gram-negative pathogens are common in COVID-19 patients and are often associated with higher mortality. This is a first ever report on the safety and efficacy of levonadifloxacin in the treatment of secondary bacterial pulmonary infections in patients with COVID-19 pneumonia.Methods: This multi-center, retrospective, post-marketing and real-world study assessed the safety and efficacy of IV and/or oral levonadifloxacin in the treatment of bacterial infections encountered in COVID-19 patients. Data for 154 male/female patients above 18 years of age who received levonadifloxacin (injectable and/or oral) was collected from 44 participating sites. Study outcomes were the clinical and microbial success at the end of therapy. Safety was assessed based on clinical and laboratory adverse events.Results: Among the 154 patients assessed, 121 (78.6%) were males and 142 (92.2%) were hospitalized. Majority of the patients (119) received all-IV therapy while 11 patients were prescribed with IV followed by oral regimen. All-oral therapy was received by 24 patients. The most common co-morbid conditions were diabetes (19.6%) and hypertension (19.2%). Post-treatment with levonadifloxacin, clinical and microbial success rates were 96.8% and 97.0% respectively.Conclusions: Levonadifloxacin showed promising safety and efficacy when used as IV and/or oral therapy for the treatment of secondary bacterial pulmonary infections in COVID-19 patients. Clinically relevant features of levonadifloxacin such as availability of both IV and oral options, broad spectrum coverage and reassuring safety in patients with significant co-morbidities could help simplify the management.Trial registration no. CTRI/2020/09/028152 [Registered on: 30/09/2020].

Vitamin K prophylaxis in newborns

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.

All-oral longer regimens are effective for the management of multidrug resistant tuberculosis in high burden settings

BackgroundRecent World Health Organisation guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline- and/or delamanid as part of their multidrug regimen.MethodsPatients with a positive baseline culture were included. Six-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods.ResultsCulture conversion was observed in 83.8% (526/628) of patients receiving an all-oral regimen and 85.5% (425/497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95%CI: 0.88–1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients.ConclusionsAmong individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.

FETO-MATERNAL OUTCOME OF INTRAVENOUS LABETALOLAND ORAL NIFEDIPINE IN SEVERE PRE-ECLAMPSIA- A COMPARATIVE STUDY

Introduction: Pre-eclampsia (PE) is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. Aims and objectives: 1. to determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. 2. To compare the time taken to reach the therapeutic goal blood pressure after using intravenous labetalol & oral nifedipine in severe pregnancy induced hypertension. 3. The time taken to achieve a blood pressure of less than 150/100 mmHg. 4. To compare the maternal and perinatal outcome among the subjects using nifedepine over labetalo. Material and method: PROSPECTIVE RANDOMISED INTERVENTIONAL COMPARITIVE TRAIL. One and half year. Conclusion: Our present study compares the efficacy of oral Nifedipine and IV Labetalol in reaching the therapeutic goal. From the results of our study we can conclude that nifedipine required less time for reaching target BP as compare to labetalol. Less no of dose of nifedipine was used for the rapid control of blood pressure in severe hypertension in pregnancy. So, Nifedipine may be preferable as it is a simple, less time and is an oral regimen.