Facilitators and barriers to reducing chemotherapy for early-stage breast cancer: a qualitative analysis of interviews with patients and patient advocates.

BACKGROUND: As the combination of systemic and targeted chemotherapies is associated with severe adverse side effects and long-term health complications, there is interest in reducing treatment intensity for patients with early-stage breast cancer (EBC). Clinical trials are needed to determine the feasibility of reducing treatment intensity while maintaining 3-year recurrence-free survival of greater than 92%. To recruit participants for these trials, it is important to understand patient perspectives on reducing chemotherapy. METHODS: We collected qualitative interview data from twenty-four patients with Stage II-III breast cancer and sixteen patient advocates. Interviews explored potential barriers and facilitators to participation in trials testing reduced amounts of chemotherapy. As the COVID-19 pandemic struck during data collection, seventeen participants were asked about the potential impact of COVID-19 on their interest in these trials. Interviews were audio-recorded and transcribed, and researchers used qualitative content analysis to code for dominant themes. RESULTS: Seventeen participants (42.5%) expressed interest in participating in a trial of reduced chemotherapy. Barriers to reducing chemotherapy included (1) fear of recurrence and inefficacy, (2) preference for aggressive treatment, (3) disinterest in clinical trials, (4) lack of information about expected outcomes, (5) fear of regret, and (6) having young children. Facilitators included (1) avoiding physical toxicity, (2) understanding the scientific rationale of reducing chemotherapy, (3) confidence in providers, (4) consistent monitoring and the option to increase dosage, (5) fewer financial and logistical challenges, and (6) contributing to scientific knowledge. Of those asked, nearly all participants said they would be more motivated to reduce treatment intensity in the context of COVID-19, primarily to avoid exposure to the virus while receiving treatment. CONCLUSIONS: Among individuals with EBC, there is significant interest in alleviating treatment-related toxicity by reducing chemotherapeutic intensity. Patients will be more apt to participate in trials testing reduced amounts of chemotherapy if these are framed in terms of customizing treatment to the individual patient and added benefit-reduced toxicities, higher quality of life during treatment and lower risk of long-term complications-rather than in terms of taking treatments away or doing less than the standard of care. Doctor-patient rapport and provider support will be crucial in this process.

De-escalation strategies for non-pharmaceutical interventions following infectious disease outbreaks: a rapid review and a proposed dynamic de-escalation framework.

BACKGROUND: The severity of COVID-19, as well as the speed and scale of its spread, has posed a global challenge. Countries around the world have implemented stringent non-pharmaceutical interventions (NPI) to control transmission and prevent health systems from being overwhelmed. These NPI have had profound negative social and economic impacts. With the timeline to worldwide vaccine roll-out being uncertain, governments need to consider to what extent they need to implement and how to de-escalate these NPI. This rapid review collates de-escalation criteria reported in the literature to provide a guide to criteria that could be used as part of de-escalation strategies globally. METHODS: We reviewed literature published since 2000 relating to pandemics and infectious disease outbreaks. The searches included Embase.com (includes Embase and Medline), LitCovid, grey literature searching, reference harvesting and citation tracking. Over 1,700 documents were reviewed, with 39 documents reporting de-escalation criteria included in the final analysis. Concepts retrieved through a thematic analysis of the included documents were interlinked to build a conceptual dynamic de-escalation framework. RESULTS: We identified 52 de-escalation criteria, the most common of which were clustered under surveillance (cited by 43 documents, 10 criteria e.g. ability to actively monitor confirmed cases and contact tracing), health system capacity (cited by 30 documents, 11 criteria, e.g. ability to treat all patients within normal capacity) and epidemiology (cited by 28 documents, 7 criteria, e.g. number or changes in case numbers). De-escalation is a gradual and bi-directional process, and resurgence of infections or emergence of variants of concerns can lead to partial or full re-escalation(s) of response and control measures in place. Hence, it is crucial to rely on a robust public health surveillance system. CONCLUSIONS: This rapid review focusing on de-escalation within the context of COVID-19 provides a conceptual framework and a guide to criteria that countries can use to formulate de-escalation plans.

Antimicrobial Stewardship during COVID-19 Outbreak: A Retrospective Analysis of Antibiotic Prescriptions in the ICU across COVID-19 Waves.

The demographics and outcomes of ICU patients admitted for a COVID-19 infection have been characterized in extensive reports, but little is known about antimicrobial stewardship for these patients. We designed this retrospective, observational study to investigate our hypothesis that the COVID-19 pandemic has disrupted antimicrobial stewardship practices and likely affected the rate of antibiotic de-escalation (ADE), patient outcomes, infection recurrence, and multidrug-resistant bacteria acquisition. We reviewed the prescription of antibiotics in three ICUs during the pandemic from March 2020 to December 2021. All COVID-19 patients with suspected or proven bacterial superinfections who received antibiotic treatment were included. The primary outcome was the rate of ADE, and secondary outcomes included the rate of appropriate empirical treatment, mortality rates and a comparison with a control group of infected patients before the COVID-19 pandemic. We included 170 COVID-19 patients who received antibiotic treatment for a suspected or proven superinfection, of whom 141 received an empirical treatment. For the latter, antibiotic treatment was de-escalated in 47 (33.3%) patients, escalated in 5 (3.5%) patients, and continued in 89 (63.1%) patients. The empirical antibiotic treatment was appropriate for 87.2% of cases. ICU, hospital, and day 28 and day 90 mortality rates were not associated with the antibiotic treatment strategy. The ADE rate was 52.2% in the control group and 27.6% in the COVID-19 group (p < 0.001). Our data suggest that empirical antibiotic treatment was appropriate in most cases. The ADE rates were lower in the COVID-19 group than in the control group, suggesting that the stress associated with COVID-19 affected our practices.

Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths.

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.

A systematic review of de-escalation strategies for redeployed staff and repurposed facilities in COVID-19 intensive care units (ICUs) during the pandemic.

BACKGROUND: Intensive care units (ICUs) experienced a surge in patient cases during the COVID-19 pandemic. Demand was managed by redeploying healthcare workers (HCWs) and restructuring facilities. The rate of ICU admissions has subsided in many regions, with the redeployed workforce and facilities returning to usual functions. Previous literature has focused on the escalation of ICUs, limited research exists on de-escalation. This study aimed to identify the supportive and operational strategies used for the flexible de-escalation of ICUs in the context of COVID-19. METHODS: The systematic review was developed by searching eight databases in April and November 2021. Papers discussing the return of redeployed staff and facilities and the training, wellbeing, and operational strategies were included. Excluded papers were non-English and unrelated to ICU de-escalation. Quality was assessed using the mixed methods appraisal tool (MMAT) and authority, accuracy, coverage, objectivity, date, and significance (AACODS) checklist, findings were developed using narrative synthesis and thematic analysis. FINDINGS: Fifteen papers were included from six countries covering wellbeing and training themes encompassing; time off, psychological follow-up, gratitude, identification of training needs, missed training catch-up, and continuation of ICU and disaster management training. Operational themes included management of rotas, retainment of staff, division of ICU facilities, leadership changes, traffic light systems, and preparation for re-expansion. INTERPRETATION: The review provided an overview of the landscape of de-escalation strategies that have taken place in six countries. Limited empirical evidence was available that evaluated the effectiveness of such strategies. Empirical and evaluative research from a larger array of countries is needed to be able to make global recommendations on ICU de-escalation practices.

Skirmishes along the Sino-Indian Border – Strategic Options for India

In the backdrop of the Covid-19 pandemic, the clash in the Galwan Valley (June 15, 2020) between the Chinese and Indian troops, that killed twenty Indian soldiers, is undoubtedly a watershed moment in India-China relations. While both the Asian giants seek to avoid war, India and China have sharpened the political rhetoric;meanwhile, troops from both sides continue to be amassed along the Line of Actual Control (LAC). The process of disengagement of troops and de-escalation of tensions have worked, albeit limitedly. Furthermore, the growing support of China to Taliban controlled Afghanistan (August 2021), will impact the course of Sino-India relations. The current stand-off between India and China marks the beginning of a new phase of relations where its repercussions will be felt in their immediate periphery and beyond. This article focuses on the strategic options for India. The transgression of China across the LAC will continue to cast its shadow over the relations between the two Asian giants. The earlier “spirit” and “connect” between the two nations stand broken and mending the same will test the institutions and leadership of both the countries. © 2021, Institute of China Studies. All rights reserved.

Optimal Staged Reopening Schedule Based on ICU Capacity: A Model-Informed Strategy

Reopening plans and strategies remain to be a top priority issue, post a pandemic wave, for economic recovery with a relatively safe community. We use a transmission dynamics model, parameterized through model fitting to cumulative incidence data during different social distancing escalation phases, to identify the optimal timing of reopening based on social-distancing de-escalation in a population. We use the Province of Ontario, Canada as a case study. The optimization is subject to the constraint that a future COVID-19 outbreak will not lead to the need of acute and intensive care unit beds beyond their local public health capacity. We minimize the cost, the total number of contacts lost until we reach a certain targeted date. We illustrate this optimization process by considering a particular de-escalation strategy that simply ‘reverses’ the escalation steps. We consider several scenarios depending on the number of de-escalation phases (characterized by an increase in the daily number of contacts), and different lengths of the period between a date when the cost is evaluated until a targeted data when the constraint is to be removed (for example, the anticipated date when a mass COVID-19 vaccination or an effective treatment becomes available) so that normal contacts prior to COVID-19 pandemic can be resumed. In the case of Ontario, we conclude that resuming 80% of pre-pandemic activity level should not happen 2 months before the vaccine/drug treatment becomes available. We also show that improving contact tracing and diagnosis capacity has a significant effect on the reopening date, whereas increasing ICU beds capacity has only a minor effect. © 2022, Springer Nature Switzerland AG.

Patient perspectives on chemotherapy de-escalation in breast cancer.

BACKGROUND: Given excellent survival outcomes in breast cancer, there is interest in de-escalating the amount of chemotherapy delivered to patients. This approach may be of even greater importance in the setting of the COVID-19 pandemic. METHODS: This concurrent mixed methods study included (1) interviews with patients and patient advocates and (2) a cross-sectional survey of women with breast cancer served by a charitable nonprofit organization. Questions evaluated interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation. RESULTS: Sixteen patient advocates and 24 patients were interviewed. Key barriers to de-escalation included fear of recurrence, worry about decision regret, lack of clinical trial interest, and dislike for focus on less treatment. Facilitators included trust in physician recommendation, toxicity avoidance, monitoring for progression, perception of good prognosis, and impact on daily life. Participants reported that the COVID-19 pandemic made them more likely to avoid chemotherapy if possible. Of 91 survey respondents, many (43%) patients would have been unwilling to participation in a de-escalation clinical trial. The most commonly reported barrier to participation was fear of recurrence (85%). Few patients (19%) considered clinical trials themselves as a barrier to de-escalation trial participation. The most popular terminology describing chemotherapy de-escalation was "lowest effective chemotherapy dose" (53%); no patients preferred the term "de-escalation." CONCLUSIONS: Fear of recurrence is a common concern among breast cancer survivors and patient advocates, contributing to resistance to de-escalation clinical trial participation. Additional research is needed to understand how to engage patients in de-escalation trials.

De-escalating cancer treatments during COVID 19 pandemic: Is metronomic chemotherapy a reasonable option?

COVID 19 pandemic represents an emergency for public health services and containment measures to reduce the risk of infection have been promptly activated worldwide. The healthcare systems reorganization has had a major impact on the management of cancer patients who are considered at high risk of infection. Recommendations and guidelines on how to manage cancer patients during COVID 19 pandemic have been published. Oral administration of chemotherapy is recommended to limit the access of cancer patients to hospital facilities and in some cases to guarantee the continuum of care. Low-dose metronomic administration of chemotherapy with different drugs and schedules has emerged in the last years as a possible alternative to conventional chemotherapy, due to its promising tumor control rates and excellent safety profiles. Moreover, given that many metronomic schedules use the oral route administration, it could represent a therapeutic strategy to ensure continuum of cancer care during COVID 19 pandemic. In this review we have selected all the clinical studies that have used the metronomic strategy, especially with oral drugs, in order to identify the subgroups of cancer patients who can benefit most from a metronomic approach even during COVID 19 pandemic.

Impact of SARS-CoV-2 lockdown and de-escalation on air-quality parameters.

The SARS-CoV-2 health crisis has temporarily forced the lockdown of entire countries. This work reports the short-term effects on air quality of such unprecedented paralysis of industry and transport in different continental cities in Spain, one of the countries most affected by the virus and with the hardest confinement measures. The study takes into account sites with different sizes and diverse emission sources, such as traffic, residential or industrial emissions. This work reports new field measurement data for the studied pandemic period and assesses the air quality parameters within the historic trend of each pollutant and site. Thus, 2013-2020 data series from ground-air quality monitoring networks have been analysed to find out statistically significant changes in atmospheric pollutants during March-June 2020 due to this sudden paralysis of activity. The results show substantial concentration drops of primary pollutants, including NOx, CO, BTX, NMHC and NH3. Particulate matter changes were smaller due to the existence of other natural sources. During the lockdown the ozone patterns were different for each studied location, depending on the VOCs-NOx ratios, with concentration changes close to those expected from the historical series in each site and not statistically attributable to the health crisis effects. Finally, the gradual de-escalation and progressive increase of traffic density within cities reflects a slow recovery of primary pollutants. The results and conclusions for these cities, with different sizes and population, and specific emission sources, may serve as a behavioural model for other continental sites and help understand future crises.

Guidance for Restarting Inflammatory Bowel Disease Therapy in Patients Who Withheld Immunosuppressant Medications During COVID-19.

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.

COVID-19 effective reproduction number dropped during Spain's nationwide dropdown, then spiked at lower-incidence regions.

COVID-19 pandemic has rapidly spread worldwide. Spain has suffered one of the largest nationwide bursts, particularly in the highly populated areas of Madrid and Barcelona (two of the five largest conurbations in Europe). We used segmented regression analyses to identify shifts in the evolution of the effective reproduction number (Rt) reported for 16 Spanish administrative regions. We associate these breaking points with a timeline of key containment measures taken by national and regional governments, applying time lags for the time from contagion to case detection, with their associated errors. Results show an early decrease of Rt that preceded the nationwide lockdown; a generalized, sharp decrease in Rt associated with such lockdown; a low impact of the strengthened lockdown, with a flattening of Rt evolution in high-incidence regions, and even increases in Rt at low-incidence regions; and an increase in Rt associated to the relaxation of the lockdown measures in ten regions. These results evidence the importance of generalized lockdown measures to contain COVID-19 spread, and the limited effect of the subsequent application of a stricter lockdown (restrictions to all non-essential economic activities). Most importantly, they highlight the importance of maintaining strong social distancing measures and strengthening public health control during lockdown de-escalation.