Anxiety and depression in cancer patients and survivors in the context of restrictions in contact and oncological care during the COVID-19 pandemic.

Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.

Early impact of treatment modifications adopted for acute lymphoblastic leukemia during SARS-CoV-2 pandemic; a single center experience and lessons for LMICs.

Treatment modifications adopted during pandemic aimed at reducing infection, myelosuppression, and optimizing hospital resources. This study evaluated outcomes for pediatric patients with ALL who had treatment modifications during pandemic compared to historical cohorts at the National Cancer Institute, Cairo University, Egypt. Bi-directional cohort study included 378 patients. Treatment modifications included omission of specific drugs or adjusting chemotherapy schedules to 6-mercaptopurine/methotrexate. Median follow-up were 45.1 and 43.2 months, for cohorts (A) and (B), respectively. The three-year overall survival were 84.9% and 87.5% (p = .48) and three-year relapse free survival were 82.8% and 86.5% (p = .11) for cohorts (A) and (B), respectively. Infection-related mortality was 11% and 4.4% for cohorts (A) and (B), respectively (p = .03). Treatment modifications adopted during the pandemic did not adversely affect the outcome of patients with ALL and notably reduced infection-related deaths. Longer follow-up is warranted to validate these findings.

Navigating uncharted waters: assessing the impact of the COVID-19 pandemic on hematopoietic stem cell transplantation: challenges and innovations.

The COVID-19 pandemic has significantly impacted hematopoietic stem cell transplantation (HSCT), necessitating adaptations across pre-transplant, transplantation, and post-transplant phases. HSCT recipients with compromised immune systems face heightened risks of severe COVID-19 outcomes, including increased mortality. The pandemic prompted significant changes in treatment strategies, with many patients experiencing delays or deferrals in autologous stem cell transplantation (ASCT), alongside adjustments to chemotherapy regimens to prevent disease recurrence. Clinical practices have evolved to address pandemic-related challenges, including a decrease in allo-HSCT procedures, a shift towards using domestic donors and peripheral blood stem cells over bone marrow grafts, and integration of telemedicine to reduce patient burden. These adaptations aim to balance COVID-19 exposure risks with the need for lifesaving HSCT. Innovations in response to the pandemic include stringent infection control measures, modified conditioning regimens, and revised post-transplant care protocols to mitigate infection risks. The importance of optimizing antiviral treatments, exploring new immunomodulatory interventions, and researching broadly neutralizing antibodies for HSCT recipients has been underscored. Despite the difficulties, the pandemic has catalyzed significant learning and innovation in HSCT practices, emphasizing the need for ongoing adaptation and research to protect this vulnerable patient population.

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. METHODOLOGY: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. RESULTS: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England's interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. CONCLUSION: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Impact of the early phase of the COVID pandemic on cancer treatment delivery and the quality of cancer care: a scoping review and conceptual model.

BACKGROUND: The disruption of health services due to coronavirus disease (COVID) is expected to dramatically alter cancer care; however, the implications for care quality and outcomes remain poorly understood. OBJECTIVE: We undertook a scoping review to evaluate what is known in the literature about how cancer treatment has been modified as a result of the COVID pandemic in patients receiving treatment for solid tumours, and what domains of quality of care are most impacted. METHODS: Citations were retrieved from MEDLINE and EMBASE (from 1 January 2019 to 28 October 2020), utilizing search terms grouped by the key concept (oncology, treatment, treatment modifications and COVID). Articles were excluded if they dealt exclusively with management of COVID-positive patients, modifications to cancer screening, diagnosis or supportive care or were not in English. Articles reporting on guidelines, consensus statements, recommendations, literature reviews, simulations or predictive models, or opinions in the absence of accompanying information on experience with treatment modifications in practice were excluded. Treatment modifications derived from the literature were stratified by modality (surgery, systemic therapy (ST) and radiotherapy) and thematically grouped. To understand what areas of quality were most impacted, modifications were mapped against the Institute of Medicine's quality domains. Where reported, barriers and facilitators were abstracted and thematically grouped to understand drivers of treatment modifications. Findings were synthesized into a logic model to conceptualize the inter-relationships between different modifications, as well as their downstream impacts on outcomes. RESULTS: In the 87 retained articles, reductions in outpatients visits (26.4%) and delays/deferrals were commonly reported across all treatment modalities (surgery: 50%; ST: 55.8% and radiotherapy: 56.7%), as were reductions in surgical capacity (57.1%), alternate systemic regimens with longer treatment intervals or use of oral agents (19.2%) and the use of hypofractionated radiotherapy regimens (40.0%). Delivery of effective, timely and equitable care was the quality domains found to be the most impacted. The most commonly reported facilitator of maintaining cancer care delivery levels was the shift to virtual models of care (62.1%), while patient-initiated deferrals and cancellations (34.8%), often due to fear of contracting COVID (60.9%), was a commonly reported barrier. CONCLUSIONS: As it will take a considerable amount of time for the cancer system to resume capacity and adjust models of care in response to the pandemic, these treatment delays and modifications will likely be prolonged and will negatively impact the quality of care and patient outcomes.

Reasons for first line ART modification over the years during the ART scale up in Uganda.

BACKGROUND: During the initial scale up of ART in sub-Saharan Africa, prescribed regimens included drugs with high potential for toxicity (particularly stavudine). More recently a growing number of patients requires second line treatment due to treatment failure, especially following the expansion of viral load testing. We aim to determine the reasons and risk factors for modification of first line ART across the years. METHODS: We included patients started on standard first line ART (2NRTI + 1 NNRTI) between 2005 and 2016 at the Infectious Diseases Institute, Kampala, Uganda. We described the reasons for treatment modification categorized in (1) toxicity (2) treatment failure (3) other reason (new TB treatment, new pregnancy). We used Cox proportional hazard to identify factors associated with treatment modification due to toxicity. RESULTS: We included 14,261 patients; 9114 (63.9%), were female, the median age was 34 years (IQR: 29-40), 60.8% were in WHO stage 3 and 4. The median BMI and CD4 count were 21.9 (IQR: 19.6-24.8) and 188 cell/µL (IQR: 65-353) respectively; 27.5% were started on stavudine, 46% on zidovudine, and 26.5% on a tenofovir containing regimens. We observed 6248 ART modifications in 4868/14,261 patients (34.1%); 1615 were due to toxicity, 1077 to treatment failure, 1330 to contraindications, and 1860 patients following WHO recommendation of phasing out stavudine and substituting with another NRTI. Modification for drug toxicity declined rapidly after the phase out of stavudine (2008), while switches to second line regimes increased after the implementation of viral load monitoring (2015). Patients with normal BMI compared to underweight, (HR: 0.79, CI 0.69-0.91), with CD4 counts 200-350 cells/µL compared to < 200 cells/µL (HR: 0.81- CI 0.71-0.93), and started on zidovudine (HR: 0.51 CI 0.44-0.59) and tenofovir (HR: 0.16, CI 0.14-0.22) compared to stavudine were less likely to have ART modification due to toxicity. Older patients (HR: 1.14 per 5-year increase CI 1.11-1.18), those in WHO stage 3 and 4 (HR: 1.19, CI 1.06-1.34) were more likely to have ART modification due to toxicity. CONCLUSIONS: Toxicity as reason for drugs substitution decreased over time mirroring the phase out of stavudine, while viral load expansion identified more patients in need of second line treatment.

Early treatment modifications improve chemotherapy adherence in ovarian cancer patients ≥70 years.

OBJECTIVE: Elderly ovarian cancer patients are underrepresented in clinical trials and disadvantaged with regard to therapeutic standards compared to other age groups. We explored the specific performance of a subset of patients aged ≥70 years in a large meta-data set of 3 phase III trials. METHODS: 3333 patients with advanced ovarian cancer recruited into 3 clinical phase III trials of the AGO & GINECO study groups were retrospectively analysed for age-specific prognostic and toxicity parameters. RESULTS: Only 10% (359/3333) of the patients were aged ≥70 years. This subgroup presented with impaired performance statuses (ECOG 2 14.8 vs 10.1%) and higher FIGO-stages (FIGO IIIC-IV 78.5 vs 73.6%) compared to younger patients. Complete operative tumor resection was achieved less frequently (postoperative tumor burden >10 mm 46.7 vs 33.9%) and elderly received less cycles of platinum/taxane-based chemotherapies (>4 cycles 81.9 vs 90.7%). FIGO-stage, histology, postoperative tumor burden and number of chemotherapy cycles were independent prognostic factors in elderly patients. Elderly patients with ≤4 cycles of chemotherapy showed a median OS of 18.4 months compared to 30.9 months in elderly with 5-6 cycles (p < 0.001). This effect was accentuated in elderly patients after complete tumor resection (cumulative survival benefit of 33.8 months). Analyses of chemotherapeutic delivery revealed that elderly patients with at least one cycle delay had higher chances to complete >4 cycles of chemotherapy. CONCLUSIONS: Protocol defined treatment modifications might support completion of >4 cycles of standard chemotherapy in fit elderly OC patients.

Utilization patterns of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus in Germany: a retrospective cohort study.

OBJECTIVE: This retrospective database analysis complements previous research to understand treatment patterns for German patients newly-initiating or switching to subsequent GLP-1 RAs. METHODS: Adult patients (≥18 years) initiating GLP-1 RA (Cohort 1 [C1]) or switching from a previous GLP-1 RA (Cohort 2 [C2]) to exenatide twice-daily (exBID), exenatide once-weekly (exQW), dulaglutide (DULA), or liraglutide (LIRA) were included in this analysis using IQVIA LRx from January 1, 2014-March 31, 2017. Patients were required to have ≥1 oral anti-hyperglycemic prescription during the 6-month pre-index period and ≥12 months follow-up. Persistence and treatment modifications were assessed within and beyond 12 months follow-up. Average daily/weekly dosage (ADD/AWD) was calculated during persistence. RESULTS: C1 included 13,417 patients, while C2 included 4,264 patients. Mean ± standard deviation (SD) age was similar (57.7 ± 11.1 years [C1], 58.9 ± 10.1 years [C2]). Most patients using DULA in C2 had switched from LIRA (56.6%). For C1, mean ADD for LIRA was 1.41 ± 0.10 mg, slightly higher in C2, and increased over time. ADD for exBID was 16.9 ± 1.0 mcg, slightly greater in C2. AWD was 2.00 ± 0.05 mg for exQW users and 1.42 ± 0.03 mg for DULA users in C1, similar to C2. For C1, 27.0% exBID, 35.3% exQW, 50.9% DULA, and 48.1% LIRA users remained persistent at 12 months. Patients using DULA had a higher probability of remaining persistent over time (Kaplan-Meier) for both cohorts. CONCLUSIONS: Patients using DULA had the highest probability of remaining persistent over time, followed by LIRA. ADD/AWD for DULA, exQW, and exBID were aligned with the recommended combination therapy dose; LIRA ADD suggests some patients use the 1.8 mg dose.

Addressing Weight Suppression to Improve Treatment Outcome for Bulimia Nervosa.

Cognitive behavioral therapy (CBT) is regarded as the gold-standard treatment for bulimia nervosa (BN), yet despite impressive empirical support for its effectiveness, over 50% of patients fail to achieve abstinence from binge eating and purging by the end of treatment. One factor that may contribute to reduced efficacy rates in CBT is weight suppression (WS; the difference between a person's highest weight ever at their adult height and current weight). A growing body of research indicates that WS in patients with BN may have a clinically significant effect on symptomatology and prognosis. However, the current cognitive behavioral framework for BN does not explicitly acknowledge the role of WS in the onset or maintenance of BN symptoms and does not provide guidance for clinicians on how to address WS during treatment. The relationship between WS, biological pressure to regain lost weight, and the maintenance of BN symptoms suggest that current cognitive behavioral models of BN may be improved by considering the role of WS and exploring needed treatment modifications. Indeed, a reconceptualization of existing models may offer insight into potential strategies that can be used to reduce the susceptibility to treatment dropout, nonresponse, and relapse. It is therefore necessary to consider whether, and how, clinicians' consideration of WS during case conceptualization and treatment planning could serve to improve CBT outcomes. The current review explores ways in which high WS could contribute to poor CBT outcomes, provides preliminary clinical recommendations for incorporating WS into existing cognitive behavioral treatments based on extant data and clinical wisdom, and proposes suggestions for future research needed in this domain.

Utilization Patterns of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus in Italy: A Retrospective Cohort Study.

INTRODUCTION: Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. METHODS: Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. RESULTS: We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day. CONCLUSIONS: This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. FUNDING: Eli Lilly and Co., Indianapolis, IN, USA.

Hospitalization Drug Regimen Changes in Geriatric Patients and Adherence to Modifications by General Practitioners in Primary Care.

OBJECTIVES: To evaluate the overall rate of adherence by general practitioners (GPs) to treatment modifications suggested at discharge from hospital and to assess the way communication between secondary and primary care could be improved. DESIGN: Observational prospective cohort study. SETTING: Patients hospitalized from the emergency department to the acute geriatric care unit of a university hospital. PARTICIPANTS: 206 subjects with a mean age of 85 years. MEASUREMENTS: Changes in drug regimen undertaken during hospitalization were collected with the associated justifications. Adherence at one month by GPs to treatment modifications was assessed as well as modifications implemented in primary care with their rationale in case of non-adherence. Community pharmacists' and GPs' opinions about quality of communication and information transfer at hospital-general practice interface were investigated. RESULTS: 5.5 ± 2.8 drug regimen changes were done per patient during hospitalization. The rate of adherence by GPs to treatment modifications suggested at discharge from hospital was 83%. In most cases, non-adherence by GPs to treatment modifications done during hospitalization was due to dosage adjustments, symptoms resolution but also worsening of symptoms. The last of which was particularly true for psychotropic drugs. All GPs received their patients' discharge letters but the timely dissemination still needs to be improved. Only 6.6% of community pharmacists were informed of treatment modifications done during their patients' hospitalization. CONCLUSION: Our findings showed a successful rate of adherence by GPs to treatment modifications suggested at discharge from hospital, due to the fact that optimization was done in a collaborative way between geriatricians and hospital pharmacists and that justifications for drug regimen changes were systematically provided in discharge letters. Communication processes at the interface between secondary and primary care, particularly with community pharmacists, must be strengthened to improve seamless care.

Lipid-lowering treatment modifications among patients with hyperlipidemia and a prior cardiovascular event: a US retrospective cohort study.

BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database. The index date was the initiation date of statins and/or ezetimibe. All patients had ≥1 medical claims related to myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, or percutaneous coronary intervention within 12 months prior to the index date. Treatment modifications to statins and/or ezetimibe initiated on the index date (index therapy) included permanent discontinuation of any lipid lowering therapy (LLT), rechallenge, switching, subtraction, augmentation, and dose changes. RESULTS: Among 17,902 patients, around 90% initiated with statin monotherapy, followed by statin and ezetimibe combination (3.0%: 18-64 years; 3.8%: ≥65 years). Ten percent or less initiated on high intensity statins. Most common treatment modifications were rechallenging index therapy (25.2%: 18-64 years, 27.0%: ≥65 years), switching (27.5%: 18-64 years, 24.6%: ≥65 years), and permanent discontinuation of any LLT (18.6%: 18-64 years, 21.0%: ≥65 years). Only 10% of patients in both groups underwent dose escalation. CONCLUSIONS: Real-world evidence indicates that few high-risk patients initiate therapy with high-intensity statins. More than 50% of patients underwent a rechallenge or switching. Despite high CVD risk profile, approximately 20% of patients permanently discontinued any LLT. Key limitations: Pharmacy claims do not provide information on whether patients who had a pharmacy fill actually took the medication as prescribed. It is unknown whether rechallenge was a simple delay in filling a prescription or an actual rechallenge of their index therapy. Reasons for treatment discontinuations or modifications were unavailable in claims data.

Regorafenib-associated hand-foot skin reaction: practical advice on diagnosis, prevention, and management.

BACKGROUND: Regorafenib is an orally available, small-molecule multikinase inhibitor with international marketing authorizations for use in colorectal cancer and gastrointestinal stromal tumors. In clinical trials, regorafenib showed a consistent and predictable adverse-event profile, with hand-foot skin reaction (HFSR) among the most clinically significant toxicities. This review summarizes the clinical characteristics of regorafenib-related HFSR and provides practical advice on HFSR management to enable health care professionals to recognize, pre-empt, and effectively manage the symptoms, thereby allowing patients to remain on active therapy for as long as possible. DESIGN: This review is based on a systematic literature search of the PubMed database (using synonyms of HFSR, regorafenib, and skin toxicities associated with targeted therapies or cytotoxic chemotherapy). However, as this search identified very few articles, the authors also use their clinical experience as oncologists and dermatologists managing patients with treatment-related HFSR to provide recommendations on recognition and management of HFSR in regorafenib-treated patients. RESULTS: Regorafenib-related HFSR is similar to that seen with other multikinase inhibitors (e.g. sorafenib, sunitinib, cabozantinib, axitinib, and pazopanib) but differs from the hand-foot syndrome seen with cytotoxic chemotherapies (e.g. fluoropyrimidines, anthracyclines, and taxanes). There have been no controlled trials of symptomatic management of regorafenib-related HFSR, and limited good-quality evidence from randomized clinical trials of effective interventions for HFSR associated with other targeted therapies. Recommendations on prevention and management of regorafenib-related HFSR in this review are therefore based on the expert opinion of the authors (dermatologists and oncologists with expertise in the management of treatment-related skin toxicities and oncologists involved in clinical trials of regorafenib) and tried-and-tested empirical experience with other multikinase inhibitors and cytotoxic chemotherapies. CONCLUSIONS: As recommended in this review, treatment modifications and supportive measures to prevent, reduce, and manage HFSR can allow patients to continue regorafenib at the optimal dose to derive benefit from treatment.