Health-related quality of life in rural cancer survivors compared with their urban counterparts: a systematic review.

PURPOSE: We conducted a systematic review to describe health-related quality of life (HRQOL) in rural cancer survivors (RCS), and compare HRQOL between RCS and urban cancer survivors (UCS). METHOD: We searched Medline, Embase, CINAHL Plus, and PsycINFO for studies with HRQOL in adult cancer survivors living in rural, regional, remote, and urban areas, who had completed definitive primary cancer treatment, without evidence of residual disease. Where available, we used normative and clinically important values to ascribe meaning to HRQOL data. FINDINGS: Fifteen studies (16 papers) were included. Most were from the US (n = 8) and reported on breast cancer survivors (n = 9). Six HRQOL instruments, collecting data across 16 domains, were used. Three instruments were specific to the survivorship phase. Normative and clinical data were available for 12 studies. Compared with normative populations, RCS had clinically worse physical HRQOL (6/12 studies), better social/family (5/7), and functional (3/6) HRQOL, and there were no differences in emotional or/mental HRQOL (9/12). In six studies with rural-urban comparator groups and normative and clinically important data, RCS and UCS had clinically worse physical (3/6 and 2/6, respectively) and better social/family (3/4 and 2/4 studies, respectively) HRQOL than normative populations. Functional HRQOL was better in RCS (2/4 studies) than UCS and normative populations. In 3/6 studies, there were no clinical differences in emotional or/mental HRQOL between RCS, UCS, and normative populations. CONCLUSION: Overall, HRQOL is not clearly better or worse in RCS than UCS. Future research should include different tumor types, rural residents, and survivorship-specific HRQOL instruments.

Development of an Embryo Toxicity Test to Assess the Comparative Toxicity of Metal Exposure on Different Life Stages of Freshwater Gastropods.

Early life stages are commonly thought to be highly sensitive to environmental contaminants and may offer insight into the future health of a population. Despite the importance of studying early life stages, very few standard protocols for benthic invertebrates commonly used in ecotoxicological assessments measure developmental endpoints. The goal of the present study was to develop and optimize a robust standard protocol for studying embryonic endpoints in freshwater gastropods. The developed method was then used to characterize the sensitivity of four embryonic endpoints (viability, hatching, deformities, and biomass production), in conjunction with juvenile and adult mortality, for the snail Planorbella pilsbryi exposed to three metals (copper [Cu], cadmium [Cd], and nickel [Ni]). Biomass production was typically the most sensitive endpoint but was relatively variable, while embryo hatching was slightly less sensitive but highly consistent for all three metals. However, no single embryonic endpoint was consistently the most sensitive, which demonstrates the importance of assessing a broad range of endpoints and life stages in ecotoxicological risk assessment. Interestingly, the embryonic life stage of P. pilsbryi was considerably less sensitive to Cu exposure compared with juvenile and adult mortality. However, for Cd exposure, embryonic endpoints were the most sensitive, and for Ni exposure, embryonic endpoints were similar in sensitivity to juvenile and adult mortality. The present study has valuable applications in conducting developmental toxicity research with organisms lacking standardized testing protocol as well as future applications in multigenerational and in silico toxicity research. Environ Toxicol Chem 2023;42:1791-1805. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Impact of COVID-19 on cancer service delivery: a follow-up international survey of oncology clinicians.

BACKGROUND: The COVID-19 pandemic has had a vast impact on cancer service delivery around the world. Previously reported results from our international survey of oncology clinicians, conducted through March-April 2020, found that clinicians reported altering management in both the curative and palliative settings and not in proportion to the COVID-19 case burden in their region of practice. This follow-up survey, conducted from 27th September to 7th November 2020, aimed to explore how attitudes and practices evolved over the 2020 pandemic period. PARTICIPANTS AND METHODS: Participants were medical, radiation and surgical oncologist and trainees. Surveys were distributed electronically via ESMO and other collaborating professional societies. Participants were asked to compare their practice prior to the pandemic to both the period of March-April 2020, referred to as the 'early' period, and the current survey period, referred to as the 'later' period. RESULTS: One hundred and seventy-two oncology clinicians completed the survey. The majority of respondents were medical oncologists (n = 136, 79%) and many were from Europe (n = 82, 48%). In the 'early' period, 88% (n = 133) of clinicians reported altering their practice compared to 63% (n = 96) in the 'later' period. Compared to prior to the pandemic, clinicians reported fewer new patient presentations in the 'early' period and a trend towards more patients presenting with advanced disease in the 'later' period. CONCLUSIONS: Results indicate a swing back towards pre-COVID-19 practices despite an increase in the rate of cumulative COVID-19 cases across 2020. The impact of these changes on cancer associated morbidity and mortality remains to be measured over the months and years to come.

A phase 1 study of nevanimibe HCl, a novel adrenal-specific sterol O-acyltransferase 1 (SOAT1) inhibitor, in adrenocortical carcinoma.

Background Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with very limited treatment options. Nevanimibe HCl (formerly ATR-101), a novel adrenal-specific sterol O-acyltransferase 1 (SOAT1) inhibitor, has been shown in nonclinical studies to decrease adrenal steroidogenesis at lower doses and to cause apoptosis of adrenocortical cells at higher doses. Methods This phase 1, multicenter, open-label study assessed the safety and pharmacokinetics (PK) of nevanimibe in adults with metastatic ACC (NCT01898715). A "3 + 3" dose-escalation design was used. Adverse events (AEs), PK, and tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were evaluated every 2 months. Results 63 patients with metastatic ACC, all of whom had previously failed systemic chemotherapy and only 2 of whom were mitotane-naïve, were dosed with oral nevanimibe at doses ranging from 1.6 mg/kg/day to 158.5 mg/kg/day. Subjects who did not experience tumor progression or a dose-limiting toxicity (DLT) could continue to receive additional cycles. No patients experienced a complete or partial response; however, 13 of the 48 (27%) patients who underwent imaging at 2 months had stable disease (SD), and 4 of these had SD > 4 months. In addition, drug-related adrenal insufficiency, considered a pharmacologic effect of nevanimibe, was observed in two patients. The most common treatment-emergent AEs were gastrointestinal disorders (76%), including diarrhea (44%) and vomiting (35%). A maximum tolerated dose (MTD) could not be defined, as very few dose-limiting toxicities (DLTs) occurred. Because the large number of tablets required at the highest dose (i.e., ~24 tablets/day) resulted in low-grade gastrointestinal adverse effects, a maximum feasible dose of 128.2 mg/kg/day was established as a dose that could be taken on a long-term basis. Conclusions This study demonstrated the safety of nevanimibe at doses of up to ~6000 mg BID. As the total number of tablets required to achieve an MTD exceeded practical administration limits, a maximum feasible dose was defined. Given that the expected exposure levels necessary for an apoptotic effect could not be achieved, the current formulation of nevanimibe had limited efficacy in patients with advanced ACC.

Variation in the time to treatment for stage III and IV non-small cell lung cancer patients for hospitals in the Netherlands.

OBJECTIVES: Increased emphasis on molecular diagnostics can lead to increased variation in time to treatment (TTT) for patients with stage III and IV non-small cell lung cancer. This article presents the variation in TTT for advanced NSCLC patients observed in Dutch hospitals before the widespread use of immunotherapy. The aim of this article was to explore the variation in TTT between patients, as well as between hospitals. MATERIAL AND METHODS: Based on the Netherlands Cancer Registry, we used patient-level data (n = 4096) from all 78 hospitals that diagnosed stage III or IV NSCLC in the Netherlands in 2016. To investigate how patient characteristics and hospital-level effects are associated with TTT (from diagnosis until start treatment), we interpreted regression model results for five common patient profiles to analyze the influence of age, gender, tumor stage, performance status, histology, and referral status as well as hospital-level characteristics on the TTT. RESULTS AND CONCLUSIONS: TTT varies substantially between and within hospitals. The median TTT was 28 days with an inter-quartile range of 22 days. The hospital-level median TTT ranges from 17 to 68 days. TTT correlates significantly with tumor stage, performance status, and histology. The hospital-level effect, unrelated to hospital volume and type, affected TTT by several weeks at most. For most patients, TTT is within range as recommended in current guidelines. Variation in TTT seems higher for patients receiving either radiotherapy or targeted therapy, or for patients referred to another hospital and we hypothesize this is related to the complexity of the diagnostic pathway. With further advances in molecular diagnostics and precision oncology we expect variation in TTT to increase and this needs to be considered in designing optimal cancer care delivery.

A scoping review of metamodeling applications and opportunities for advanced health economic analyses.

INTRODUCTION: Metamodels, also known as meta-models, surrogate models, or emulators, are used in several fields of research to negate runtime issues with analyzing computational demanding simulation models. This study introduces metamodeling and presents results of a review on metamodeling applications in health economics. AREAS COVERED: A scoping review was performed to identify studies that applied metamodeling methods in a health economic context. After search and selection, 13 publications were found to employ metamodeling methods in health economics. Metamodels were used to perform value of information analysis (n = 5, 38%), deterministic sensitivity analysis (n = 4, 31%), model calibration (n = 1, 8%), probabilistic sensitivity analysis (n = 1), or optimization (n = 1, 8%). One study was found to extrapolate a simulation model to other countries (n = 1, 8%). Applied metamodeling techniques varied considerably between studies, with linear regression being most frequently applied (n = 7, 54%). EXPERT COMMENTARY: Although it has great potential to enable computational demanding analyses of health economic models, metamodeling in health economics is still in its infancy, as illustrated by the limited number of applications and the relatively simple metamodeling methods applied. Comprehensive guidance specific to health economics is needed to provide modelers with the information and tools needed to utilize the full potential of metamodels.

Incidence and prognostic factors of chronic pain after isolated musculoskeletal extremity injury.

BACKGROUND: Chronic pain in patients is usually related to an episode of pain following acute injury, emphasizing the need to prevent progression from acute to chronic pain. Multiple factors in the acute phase might be responsible for perpetuating the pain. The presentation of patients at the emergency department (ED) presents a prime opportunity to identify patients at high risk for chronic pain and to start appropriate treatment. METHODS: The PROTACT study is a prospective follow-up study aiming to estimate the incidence and prognostic factors responsible for the development of chronic pain after musculoskeletal injury. Data including sociodemographic, pain, clinical, injury- or treatment-related and psychological factors of 435 patients were collected from registries and questionnaires at ED visit, 6-week, 3- and 6-month follow-up. RESULTS: At 6 months post-injury, 43.9% of the patients had some degree of pain (Numeric Rating Scale (NRS) ≥1) and 10.1% had chronic pain (NRS ≥4). Patients aged over 40 years, in poor physical health, with pre-injury chronic pain, pain catastrophizing, high urgency level and severe pain at discharge were found to be at high risk for chronic pain. CONCLUSIONS: Two prognostic factors, severe pain at discharge and pain catastrophizing, are potentially modifiable. The implementation of a pain protocol in the ED and the use of cognitive-behavioural techniques involving reducing catastrophizing might be useful.

Individual risk profiling for breast cancer recurrence: towards tailored follow-up schemes.

BACKGROUND: Breast cancer follow-up is not tailored to the risk of locoregional recurrences (LRRs) in individual patients or as a function of time. The objective of this study was to identify prognostic factors and to estimate individual and time-dependent LRR risk rates. METHODS: Prognostic factors for LRR were identified by a scoping literature review, expert consultation, and stepwise multivariate regression analysis based on 5 years of data from women diagnosed with breast cancer in the Netherlands in 2005 or 2006 (n=17,762). Inter-patient variability was elucidated by examples of 5-year risk profiles of average-, medium-, and high-risk patients, whereby 6-month interval risks were derived from regression estimates. RESULTS: Eight prognostic factors were identified: age, tumour size, multifocality, gradation, adjuvant chemo-, adjuvant radiation-, hormonal therapy, and triple-negative receptor status. Risk profiles of the low-, average-, and high-risk example patients showed non-uniform distribution of recurrence risks (2.9, 7.6, and 9.2%, respectively, over a 5-year period). CONCLUSION: Individual risk profiles differ substantially in subgroups of patients defined by prognostic factors for recurrence and over time as defined in 6-month time intervals. To tailor follow-up schedules and to optimise allocation of scarce resources, risk factors, frequency, and duration of follow-up should be taken into account.

Differential cortical activation during observation and observation-and-imagination.

The activity of the brain during observation or imagination of movements might facilitate the relearning of motor functions after stroke. The present study examines whether there is an additional effect of imagination over observation-only. Eight healthy subjects observed and observed-and-imagined a movement of a hand; 64-channel EEG was used to measure brain activity. The synchronization of the theta (4-8 Hz), alpha (8-13 Hz) and beta (13-25 Hz) frequency bands was calculated and plotted in topoplots. The temporal changes of the sensorimotor area (C3, C4) and the centro-parietal cortex (Pz) were analyzed in the two experimental conditions. During observation-and-imagination, a significant larger desynchronization (p = 0.004) in the sensorimotor area was found compared to observation-only in all electrodes and frequency bands. In addition, temporal differences were found between observation and observation-and-imagination in the alpha frequency bands. During observation-and-imagination, modulations of EEG rhythms were stronger than during observation-only in the theta, alpha and beta frequency bands and during almost the whole activity fragment. These findings suggest an additive effect of imagination to observation in the rehabilitation after stroke.

Patient preferences for next generation neural prostheses to restore bladder function.

STUDY DESIGN: A survey administered to 66 individuals with spinal cord injury (SCI) implementing a choice-based conjoint (CBC) analysis. Six attributes with three levels each were defined and used to generate choice sets with treatment scenarios. Patients were asked to choose the scenario that they preferred most. OBJECTIVES: To determine the utility weights for treatment characteristics as well as the overall preference for the three types of neural prostheses (NP), that is Brindley, rhizotomy-free Brindley, and pudendal nerve stimulation. Earlier studies have revealed the importance of restoration of bladder function, but no studies have been performed to determine the importance of NP features. SETTING: Two academic affiliated medical systems' SCI outpatient and inpatient rehabilitation programs, Cleveland, OH. METHODS: CBC analysis followed by multinomial logit modeling. Individual part-worth utilities were estimated using hierarchical Bayes. RESULTS: Side effects had the greatest significant impact on subject choices, followed by the effectiveness on continence and voiding. NPs with rhizotomy-free sacral root stimulation were preferred (45% first choice) over pudendal afferent nerve stimulation (39% second choice) and sacral root stimulation with rhizotomy (53% third choice). Almost 20% did not want to have an NP at all times. CONCLUSION: CBC has shown to be a valuable tool to support design choices. The data showed that persons would prefer a bladder NP with minimally invasive electrodes, which would give them complete bladder function, with no side effects and that can be operated by pushing a button and they do not have to recharge themselves.

Combined retrospective analysis of seven phase II and III trials of the efficacy of linezolid in the treatment of pneumonia caused by multidrug-resistant Streptococcus pneumoniae.

BACKGROUND: Antimicrobial resistance among Streptococcus pneumoniae is of concern. Up to 30% of pneumococcal isolates worldwide are multidrug resistant. OBJECTIVE: The objective of this analysis was to assess the effectiveness of linezolid for the treatment of pneumonia caused by S pneumoniae, including multidrug-resistant S pneumoniae (MDRSP). METHODS: Data from 7 Phase II and III clinical trials that assessed the efficacy of linezolid in community- or hospital-acquired pneumonia were pooled. Adults and children (aged ≤12 years) received linezolid 600 mg and 10 mg/kg, respectively, IV or PO q12h for 7 to 14 days, with the exception of patients with documented bacteremia who could be treated for up to 28 days. Patients with a confirmed baseline isolate of S pneumoniae, including MDRSP, were assessed for clinical and microbiological outcomes. MDRSP was defined as an isolated strain of S pneumoniae that was resistant to ≥3 classes of antibiotics. Clinical cure was defined as the resolution of clinical signs and symptoms of pneumonia compared with baseline, with either improvement or absence of progression of abnormalities on chest radiography. Microbiological eradication was defined as documented or presumed eradication at the test-of-cure (TOC) visit. Results from patients with indeterminate or missing outcomes at TOC were not included in the analyses. RESULTS: Of the patients with no bacteremia and treated with linezolid, 19 adults had MDRSP and 165 had non-MDRSP, and 3 children had MDRSP and 7 had non-MDRSP. Clinical cure and microbiological eradication rates were not significantly different between those infected with an MDRSP or non-MDRSP pathogen, respectively, in adults (16/19 [84%] and 150/164 [91%]) and children (3/3 [100%] and 7/7 [100%]). CONCLUSION: Linezolid was efficacious for the treatment of pneumonia caused by S pneumoniae, including multidrug-resistant strains.