Exploring the Point-of-Sale Among Vape Shops Across the United States: Audits Integrating a Mystery Shopper Approach.

INTRODUCTION: Vape shops represent prominent, unique retailers, subject to Food and Drug Administration (FDA) regulation in the United States. AIMS AND METHODS: This study assessed compliance of US vape shop retail marketing strategies with new regulations (eg, required age verification, prohibited free samples) and pre-implementation conditions for other regulations (eg, health warning labels on all nicotine products, required disclosures of e-liquid contents). RESULTS: 95.0% of shops displayed minimum-age signage; however, mystery shoppers were asked for age verification at 35.6% upon entry and at 23.4% upon purchase. Although 85.5% of shops had some evidence of implementing FDA health warnings, 29.1% had signage indicating prohibited health claims, 16.3% offered free e-liquid samples, 27.4% had signage with cartoon imagery, and 33.3% were within two blocks of schools. All shops sold open-system devices, 64.8% sold closed-system devices, 68.2% sold their own brand of e-liquids, 42.5% sold e-liquids containing cannabidiol, 83.2% offered price promotions of some kind, and 89.9% had signage for product and price promotions. CONCLUSIONS: Results indicated that most shops complied with some implementation of FDA health warnings and with free sampling bans and minimum-age signage. Other findings indicated concerns related to underage access, health claims, promotional strategies, and cannabidiol product offerings, which call for further FDA and state regulatory/enforcement efforts.

Capacity of patients with brain metastases to make treatment decisions.

OBJECTIVE: The aim of this study was to investigate medical decision-making capacity (MDC) in patients with brain metastases. METHODS: Participants were 41 adults with brain metastases with Karnofsky Performance Status scores of ≥70 who were recruited from an academic medical center and 41 demographically matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS: The brain metastasis patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION: When defining capacity compromise as performance ≤1.5 standard deviation below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population.

Cognition in patients with newly diagnosed brain metastasis: profiles and implications.

Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis.

A prospective study of cognitive function in men with non-seminomatous germ cell tumors.

OBJECTIVE: Longitudinal neuropsychological assessments were performed to determine if adjuvant chemotherapy was associated with cognitive dysfunction in men with non-seminomatous germ cell tumors (NSGCT). METHODS: Patients with NSGCT status post-orchiectomy that either received adjuvant chemotherapy (n = 55) or did not (n = 14) were recruited. Patients were tested before chemotherapy, 1 week post-chemotherapy (or 3 months later in the surveillance group) and 12 months after the baseline evaluation. RESULTS: Compared with the surveillance group, patients treated with chemotherapy had higher rates of cognitive decline at 12 months (overall cognitive decline: 0%, 52%, and 67% in the surveillance, low exposure (LE), and high exposure (HE) group, respectively), greater number of tests that declined (mean of 0.1, 1.4, and 2.0 in the surveillance, LE, and HE group, respectively), and more frequent worsening in motor dexterity (0%, 48%, and 46% in the surveillance, LE, and HE group, respectively). Compared with the surveillance group, patients receiving more cycles of chemotherapy demonstrated worse psychomotor speed and learning and memory. Younger age was associated with greater incidence of overall cognitive decline at 12-month follow-up. CONCLUSIONS: Men with NSGCT that received chemotherapy demonstrated greater rates of cognitive decline in a dose-response manner. Reductions in motor dexterity were most common. Decline in learning and memory also was evident particularly at later follow-up time points and in men receiving more chemotherapy. Men that receive chemotherapy for NSGCT are at risk for cognitive decline and may benefit from monitoring and referral for psychosocial care.

Preservation of neurocognitive function and local control of 1 to 3 brain metastases treated with surgery and carmustine wafers.

BACKGROUND: Neurosurgical resection and whole-brain radiation therapy (WBRT) are accepted treatments for single and oligometastatic cancer to the brain. To avoid the decline in neurocognitive function (NCF) linked to WBRT, the authors conducted a prospective, multicenter, phase 2 study to determine whether surgery and carmustine wafers (CW), while deferring WBRT, could preserve NCF and achieve local control (LC). METHODS: NCF and LC were measured in 59 patients who underwent resection and received CW for a single (83%) or dominant (oligometastatic, 2 to 3 lesions) metastasis and received stereotactic radiosurgery (SRS) for tiny nodules not treated with resection plus CW. Preservation of NCF was defined as an improvement or a decline ≤ 1 standard deviation from baseline in 3 domains: memory, executive function, and fine motor skills, evaluated at 2-month intervals. RESULTS: Significant improvements in executive function and memory occurred throughout the 1-year follow-up. Preservation or improvement of NCF occurred in all 3 domains for the majority of patients at each of the 2-month intervals. NCF declined in only 1 patient. The chemowafers were well tolerated, and serious adverse events were reversible. There was local recurrence in 28% of the patients at 1-year follow-up. CONCLUSIONS: Patients with brain metastases had improvements in their cognitive trajectory, especially memory and executive function, after treatment with resection plus CW. The rate of LC (78%) was comparable to historic rates of surgery with WBRT and superior to reports of WBRT alone. For patients who undergo resection for symptomatic or large-volume metastasis or for tissue diagnosis, the addition of CW can be considered as an option.

Phase I and pharmacokinetic study of 3'-C-ethynylcytidine (TAS-106), an inhibitor of RNA polymerase I, II and III,in patients with advanced solid malignancies.

BACKGROUND: TAS-106 is a novel nucleoside analog that inhibits RNA polymerases I, II and II and has demonstrated robust antitumor activity in a wide range of models of human cancer in preclinical studies. This study was performed to principally evaluate the feasibility of administering TAS-106 as a bolus intravenous (IV) infusion every 3 weeks. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of TAS-106 as a single bolus IV infusion every 3 weeks. Plasma and urine sampling were performed during the first course to characterize the pharmacokinetic profile of TAS-106 and assess pharmacodynamic relationships. RESULTS: Thirty patients were treated with 66 courses of TAS-106 at eight dose levels ranging from 0.67-9.46 mg/m(2). A cumulative sensory peripheral neuropathy was the principal dose-limiting toxicity (DLT) of TAS-106 at the 6.31 mg/m(2) dose level, which was determined to be the maximum tolerated dose (MTD). Other mild-moderate drug-related toxicities include asthenia, anorexia, nausea, vomiting, myelosuppression, and dermatologic effects. Major objective antitumor responses were not observed. The pharmacokinetics of TAS-106 were dose-proportional. The terminal elimination half-life (t(1/2)) averaged 11.3 ± 3.3 h. Approximately 71% of TAS-106 was excreted in the urine as unchanged drug. Pharmacodynamic relationships were observed between neuropathy and: C(5min;) AUC(0-inf;) and dermatologic toxicity. CONCLUSIONS: The recommended phase II dose of TAS-106 is 4.21 mg/m(2). However, due to a cumulative drug-related peripheral sensory neuropathy that proved to be dose-limiting, further evaluation of this bolus every 21 day infusion schedule will not be pursued and instead, an alternate dosing schedule of TAS-106 administered as a continuous 24-hour infusion will be explored to decrease C(max) in efforts to minimize peripheral neuropathy and maximize antitumor activity.

Refining endpoints in brain tumor clinical trials.

As targeted therapies advance treatment for brain tumors, standard clinical trial endpoints of survival, progression free survival and radiographic response have become insufficient to capture clinical benefit. Brain cancer is a malignancy with neurodegenerative features. In this setting prolongation of life and/or radiographic stability are less clinically meaningful if neurocognitive function substantially declines. Hence evaluation of new therapeutic strategies should routinely include periodic assessment of neurocognitive function.

Using principles of learning to inform language therapy design for children with specific language impairment.

BACKGROUND: Language treatment for children with specific language impairment (SLI) often takes months to achieve moderate results. Interventions often do not incorporate the principles that are known to affect learning in unimpaired learners. AIMS: To outline some key findings about learning in typical populations and to suggest a model of how they might be applied to language treatment design as a catalyst for further research and discussion. METHODS & PROCEDURES: Three main principles of implicit learning are reviewed: variability, complexity and sleep-dependent consolidation. After explaining these principles, evidence is provided as to how they influence learning tasks in unimpaired learners. Information is reviewed on principles of learning as they apply to impaired populations, current treatment designs are also reviewed that conform to the principles, and ways in which principles of learning might be incorporated into language treatment design are demonstrated. MAIN CONTRIBUTION: This paper provides an outline for how theoretical knowledge might be applied to clinical practice in an effort to promote discussion. CONCLUSIONS & IMPLICATIONS: Although the authors look forward to more specific details on how the principles of learning relate to impaired populations, there is ample evidence to suggest that these principles should be considered during treatment design.

Differences and Similarities in the Perception of Voice Gender for Individuals Who are or are not Members of the LGBT+ Community.

PURPOSE: Compared to transgender individuals, cisgender men and women perceived "male" and "female" voices differently when using a forced-choice task with binary terms. Here, we compared individuals' perceptions of voice gender due to the influence of their own gender and/or sexuality using a rating scale rather than a forced-choice scenario. METHODS: Fifty-five participants (cisgender, transgender, and non-binary adults) listened to vocal recordings of four cisgender men and four cisgender women speakers (some recordings were pitch shifted resulting in 12 unique voice conditions) and rated the voices on a 7-point Likert scale ranging from masculine (1) to feminine (7). Likert ratings and reaction time of responses were recorded and analyzed. For a small subset of recordings, participants provided terms to describe the gender of the recorded voices. RESULTS: For the Likert voice gender rating task, there was a significant effect of gender for two out of twelve conditions. There were no significant effects of sexuality on any of the conditions. For reaction time (RT), there was no significant effect of gender for any conditions. There was no significant effect for sexuality when one subject was removed (for one condition). The number of vocabulary terms used to describe gender was significantly higher for LGBT+ participants, who used significantly more descriptive terms than those who identified as cisgender and heterosexual. DISCUSSION: Cisgender heterosexual speech-language pathologists working with transgender/non-binary clients can be more confident that their conceptualization and perception of voice gender are likely to align with that of their clients. Clinicians should utilize continuum terms (masculine, feminine) rather than the binary terms (male, female). Training of speech-language pathologists should include increasing awareness and knowledge of the perspectives and terminology used by members of the LGBT+ community with the aim of improving future clinician-client communication.

Adverse Childhood Experiences and Overdose: Lessons From Overdose Data to Action.

INTRODUCTION: Adverse childhood experiences and overdose are linked in a cycle that affects individuals and communities across generations. The Centers for Disease Control and Prevention's Overdose Data to Action cooperative agreement supports a comprehensive public health approach to overdose prevention and response activities across the U.S. Exposure to traumatic events during childhood can increase the risk for myriad health outcomes, including overdose; therefore, many Overdose Data to Action recipients leveraged funds to address adverse childhood experiences. METHODS: In 2021, an inventory of Overdose Data to Action‒funded activities implemented in 2019 and 2020 showed that 34 of the 66 recipients proposed overdose prevention activities that support people who have experienced adverse childhood experiences or that focus on preventing the intergenerational transmission of adverse childhood experiences. Activities were coded by adverse childhood experience prevention strategy, level of the social ecology, and whether they focused on neonatal abstinence syndrome. RESULTS: Most activities among Overdose Data to Action recipients occurred at the community level of the social‒ecologic model and under the intervene to lessen harms adverse childhood experience prevention strategy. Of the 84 adverse childhood experience‒related activities taking place across 34 jurisdictions, 44 are focused on neonatal abstinence syndrome. CONCLUSIONS: Study results highlight the opportunities to expand the breadth of adverse childhood experience prevention strategies across the social ecology. Implementing cross-cutting overdose and adverse childhood experience‒related activities that span the social‒ecologic model are critical for population-level change and have the potential for the broadest impact. Focusing on neonatal abstinence syndrome also offers a unique intervention opportunity for both adverse childhood experience and overdose prevention.

Speech, Language, and Communication Deficits and Intervention in a Single Case of Pediatric Autoimmune Encephalitis.

Purpose The current literature on pediatric autoimmune encephalitis (AE) focuses on medical identification/diagnosis and medical treatments. Data about the identification and treatment of communication disorders in these children are limited. This clinical focus article provides an example of the speech, language, and communication characteristics, intervention, and recovery of a single child with medical diagnoses of pediatric AE and pediatric acute-onset neuropsychiatric syndrome (PANS) and special education eligibility under the autism spectrum disorder category. Method This is an in-depth illustrative/descriptive case study. Medical, educational, and speech-language documentation of one child diagnosed with AE at age 7 years was reviewed. Methods included interviews with family members, teachers, and the school speech-language pathologist and reviews of documentation including evaluations, reports, and Individualized Education Programs. Results This child received special education and therapy services through his public school and a university speech-language clinic. He concurrently received medical treatment for AE and PANS. Comprehensive augmentative and alternative communication (AAC) intervention included the use of core words, modeling, parallel talk, self-talk, expansive recasts, shared book reading, family counseling, and collaboration with the parents and the school speech-language pathologist. The child made progress on all goals despite irregular attendance to therapy due to medical complications. Discussion Because experimental research including this population is currently limited, this descriptive case study provides valuable information to clinicians, educators, pediatricians, medical diagnosticians, and anyone providing services to a child with a complex neuropsychological disorder like AE. Future research is needed with more children who have AE, especially experimental investigations of the intervention methods utilized here. Additional research of more children with AE can provide information about the scope and severity of speech, language, and communication needs and the trajectory of recovery given AAC intervention.

Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.

BACKGROUND: It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. METHODS: Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. FINDINGS: After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. INTERPRETATION: Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.

The Brabant study: design of a large prospective perinatal cohort study among pregnant women investigating obstetric outcome from a biopsychosocial perspective.

BACKGROUND: Pregnancy is characterised by many biological and psychosocial changes. Adequate maternal thyroid function is important for the developing fetus throughout gestation. Latent class analyses recently showed three different patterns of change in thyroid function throughout pregnancy with different associations with obstetric outcome. Maternal distress during the pregnancy (anxiety and depression) negatively affects obstetric outcome. Pregnancy distress in turn may be affected by personality traits and attachment styles. Moreover, during the pregnancy, substantial social changes occur in the partner relationship and work experience. The aim of the Brabant study is to investigate the association between thyroid function trajectories and obstetric outcomes. Moreover, within the Brabant study, we will investigate how different trajectories of pregnancy distress are related to obstetric outcome, and the role of personality in this association. We will evaluate the possible role of maternal distress and attachment style on maternal-fetal bonding. Finally, we will study social changes in the perinatal period regarding partner relationship and well-being and performance at work. METHODS AND ANALYSIS: The Brabant study is a longitudinal, prospective cohort study of an anticipated 4000 pregnant women. Women will be recruited at 8-10 weeks gestation among community midwife practices in South-East Brabant in the Netherlands. Thyroid function parameters (TSH and fT4), thyroid peroxidase antibody and human chorionic gonadotrophin will be assessed at 12, 20 and 28 weeks gestation. Moreover, at these three time points women will fill out questionnaires assessing demographic and obstetric features, life style habits and psychological and social variables, such as depressive symptoms, personality, partner relationship quality and burnout. Data from the obstetric records will also be collected. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethical Committee of the Máxima Medical Center Veldhoven. Results will be submitted to peer-reviewed journals in the relevant fields and presented on national and international conferences.

Vape shop owners'/managers' attitudes about CBD, THC, and marijuana legal markets.

Over the past decade in the US there have been marked pivotal changes in the policy and retail environment regarding cannabinoids, particularly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). Many vape shops may carry products relevant to these two markets. This study interviewed vape shop owners/managers to assess their perceptions of consumer interests/behaviors regarding CBD and THC and of the impact of legalized marijuana retail on vape shops. The current study involved phone-based semi-structured interviews of 45 vape shop owners/managers in six metropolitan statistical areas (MSAs; Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, and Seattle) during Summer 2018. Overall, 82.2% of participants were male, 77.8% were non-Hispanic White, 64.4% were managers, 8.9% reported past 30-day smoking, and 95.6% reported past 30-day vaping. Overall, 44.4% sold e-liquids containing CBD. Vape shop owners/managers indicated minimal perceived risk and some beliefs in therapeutic benefits of CBD products; however, there was a broader range of perspectives regarding marijuana retail and selling marijuana for recreational use. Some chose to distance themselves from marijuana products, their use, and the possibility of entering marijuana retail if it were to evolve in their state, while some indicated high levels of enthusiasm for the growing retail marijuana market. Future research should examine how vape shops and other retailers of CBD and marijuana communicate with consumers about products and modes of using such products, as well as how various industry sectors (e.g., vape shops) adapt or evolve with increasing regulation of nicotine and increasing legalization of marijuana retail.

Vape shop identification, density and place characteristics in six metropolitan areas across the US.

Vaping is increasingly prevalent and controversial. Vape shops and convenience stores are common but distinct sources of vaping products, and where they locate may reflect likely target markets. This study examined the density and neighborhood demographics of vape shops and convenience stores in six metropolitan statistical areas (MSAs): Atlanta, Boston, Minneapolis, Oklahoma City, San Diego, Seattle. We identified 459 vape shops using Yelp and Google application programming interfaces and 10,777 convenience stores using ReferenceUSA and Dun & Bradstreet. Retailers were geocoded to census tracts (n = 4,442), and logistic regressions were conducted using as predictors percent non-White, percent youth (5-17 years or 5-20 years), and median household income from the American Community Survey, 2013-2017. Per 10,000 young adults, vape shop density ranged from 0.6 (Boston, San Diego) to 1.7 (Oklahoma City), and convenience store density ranged from 12.6 (San Diego) to 26.3 (Oklahoma City). Logistic regressions indicated that vape shops more likely resided in tracts with lower percentages of youth in Boston, but higher percentages of youth in Atlanta, as well as with lower incomes in Boston and Seattle. Convenience stores more likely resided in tracts with lower percentages of non-Whites in Atlanta and Boston; lower incomes in Atlanta, Boston, San Diego, and Seattle; and higher percentages of youth in Atlanta, Boston, and Minneapolis. These common retail sources of vaping products differentially locate in relation to neighborhood sociodemographics across MSAs. Findings suggest that, in some MSAs, vape shops and convenience stores may target youth and lower income populations.

Cognitive effects of pegylated interferon in individuals with primary brain tumors.

Cognitive changes associated with interferon treatment include impaired verbal memory, attention, processing speed, and executive functioning. Pegylated interferon is a relatively new, long-lasting form of interferon alpha, but data regarding its cognitive effects in brain tumor patients are limited. Participants in this study were 35 primary brain tumor patients who received pegylated interferon at tumor recurrence. A neuropsychological battery assessed verbal memory, executive functioning, attention, information processing speed, and language functioning. Individual growth curve analyses were used to estimate cognitive change throughout treatment with interferon. Results revealed performance declined on a task of psychomotor speed and upper extremity dexterity. Although decline in a few tests was found, its degree may have been reduced because individuals were tested after tumor recurrence where a substantial amount of cognitive change had already potentially occurred due to surgery, radiation therapy, and chemotherapy. Thus, participants may not have been starting at their baseline cognitive status and the potential neurotoxic effects of interferon may have been obscured by prior treatments. An alternative explanation, however, is that treatment with pegylated interferon did not produce further impairment and patients experienced stability in their cognitive functioning.

Cognitive and affective sequelae of primary hyperparathyroidism and early response to parathyroidectomy.

Cognitive and affective complaints are common in patients with primary hyperparathyroidism (PHPT), but few studies have used psychometric testing to document these symptoms and their response to parathyroidectomy. The current study sought to clarify the nature of cognitive and affective impairments in PHPT and changes postparathyroidectomy. One hundred eleven patients with PHPT underwent neuropsychological evaluation prior to parathyroidectomy with 68 returning for an early postsurgical evaluation. Changes in cognition were assessed using practice effect corrected reliable change indices. Biochemical and anesthesia variables were compared between groups who improved and declined. In a subset of patients, assessment revealed a significant pattern of cognitive slowing, reductions in psychomotor speed, memory impairment, and depression prior to parathyroidectomy. Postsurgical evaluations revealed a trend for improvements on timed tests and depression but a decline in memory. Older patients responded less well to surgical intervention, as did patients who experienced more dramatic changes in biochemical status following surgery. Cognitive changes early postparathyroidectomy are characterized by improved information processing speed and decline in verbal memory, with younger patients more likely to recover during this acute phase. The need for longer-term follow-up studies and increasing utilization of neuropsychological assessments in this population are discussed.

The association of health-related quality of life and cognitive function in patients receiving memantine for the prevention of cognitive dysfunction during whole-brain radiotherapy.

BACKGROUND: This study evaluated the association between health-related quality of life (HRQOL) and cognition in patients receiving memantine for prevention of cognitive dysfunction during whole-brain radiotherapy (WBRT). METHODS: Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine, 20 mg per day, within 3 days of initiating radiotherapy, for 24 weeks. The Functional Assessment of Cancer Therapy-Brain module (FACT-Br) and Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C) were completed in coordination with serial standardized tests of cognitive function. RESULTS: Of the 508 eligible patients, 442 (87%) consented to participate in the HRQOL portion and contributed to baseline analyses. Evaluable patients at 24 weeks (n = 246) included surviving patients completing FACT-Br, MOS-C, and objective cognitive assessments (n = 146, 59%) and patients alive at time of missed assessment (n = 100, 41%). Baseline cognitive function correlated significantly with FACT-Br and MOS-C self-reports. All domains of objective cognitive function showed declines over time. Neither FACT-Br nor MOS-C differed between the treatment arms. Emotional and functional well-being subscales of the FACT improved over time while the remainder of the FACT-Br domains remained stable. MOS-C scores declined over time. CONCLUSION: Baseline cognitive function correlated significantly with FACT-Br and MOS-C scores. No by-arm differences in HRQOL were observed despite differences in objective cognitive function. Patient attrition and poor testing compliance remain significant problems in studies of cognitive function of brain metastases patients and further effort is needed to improve compliance with testing and sensitivity of patient-reported measures.

Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy.

Standard oncological therapies, such as chemotherapy and cranial radiotherapy, frequently result in a spectrum of neurocognitive deficits that includes impaired learning, memory, attention, and speed of information processing. In addition to classical mechanisms of neurotoxicity associated with chemo- and radiotherapy, such as radiation necrosis and leukoencephalopathy, damage to dynamic progenitor cell populations in the brain is emerging as an important etiologic factor. Radiation- and chemotherapy-induced damage to progenitor populations responsible for maintenance of white matter integrity and adult hippocampal neurogenesis is now believed to play a major role in the neurocognitive impairment many cancer survivors experience.