Medical care disruptions during the first six months of the COVID-19 pandemic: the experience of older breast cancer survivors.

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.

Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors.

BACKGROUND: Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. DESIGN: This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. RESULTS: Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. CONCLUSIONS: CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer.

Predictors of duloxetine response in patients with oxaliplatin-induced painful chemotherapy-induced peripheral neuropathy (CIPN): a secondary analysis of randomised controlled trial - CALGB/alliance 170601.

Duloxetine is an effective treatment for oxaliplatin-induced painful chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. The objective of this secondary and exploratory analysis was to identify predictors of duloxetine response in patients with painful oxaliplatin-induced CIPN. Patients (N = 106) with oxaliplatin-induced painful CIPN were randomised to receive duloxetine or placebo. Eligible patients had chronic CIPN pain and an average neuropathic pain score ≥4/10. Duloxetine/placebo dose was 30 mg/day for 7 days, then 60 mg/day for 4 weeks. The Brief Pain Inventory-Short Form and the EORTC QLQ-C30 were used to assess pain and quality of life, respectively. Univariate and multiple logistic regression analyses were performed to identify demographic, physiologic and psychological predictors of duloxetine response. Higher baseline emotional functioning predicted duloxetine response (≥30% reduction in pain; OR 4.036; 95% CI 0.999-16.308; p = 0.050). Based on the results from a multiple logistic regression using patient data from both the duloxetine and placebo treatment arms, duloxetine-treated patients with high emotional functioning are more likely to experience pain reduction (p = 0.026). In patients with painful, oxaliplatin-induced CIPN, emotional functioning may also predict duloxetine response. ClinicalTrials.gov, Identifier NCT00489411.

Medical Care Disruptions During the First Six-Months of the COVID19 Pandemic: The Experience of Older Breast Cancer Survivors.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. RESULTS: There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. CONCLUSIONS: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Cancer and cancer-therapy related cognitive dysfunction: an international perspective from the Venice cognitive workshop.

A subset of survivors has cognitive impairment after cancer treatment. This is generally subtle, but may be sustained. In October 2006, the second international cognitive workshop was held in Venice. The workshop included neuropsychologists, clinical and experimental psychologists, medical oncologists, imaging experts, and patient advocates. The main developments since the first Cognitive Workshop in 2003 have been the following. (i) studies evaluating cognitive function in patients receiving chemotherapy for cancers other than breast cancer, and in patients receiving hormonal therapy for cancer. (ii) The publication of longitudinal prospective studies which have shown that some patients already exhibit cognitive impairment on neuropsychological testing before receiving chemotherapy, and some patients have deterioration in cognitive functioning from pre- to postchemotherapy. (iii) Studies of the underlying mechanisms of cognitive impairment both in patients and in animal models. (iv) Use of structural and functional imaging techniques to study changes in brain morphology and activation patterns associated with chemotherapy. (v) At present cognitive research in cancer is limited by methodological challenges and the lack of standardization in neuropsychological studies. The current workshop addressed many of these issues and established an international task force to provide guidelines for future research and information on how best to manage these symptoms.

Psychologic and neuropsychologic impact of autologous bone marrow transplantation.

PURPOSE: The major purpose of the current study was to evaluate the psychologic and neuropsychologic functioning of patients undergoing treatment with autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Fifty-four patients with hematologic disorders or breast cancer completed a battery of psychologic and neuropsychologic tests before ABMT, at mid-treatment (1 to 3 days following bone marrow reinfusion), and predischarge (within 1 to 2 days before discharge from the hospital). RESULTS: Analysis of pretransplant data showed significantly higher scores on the State-Trait Anxiety Inventory (STAI) and Profile of Mood States (POMS) for patients with hematologic disorders as compared with patients with breast cancer. However, no baseline differences on neuropsychologic measures were found when patients were divided into groups based on prior exposure to cranial radiation and/or intrathecal chemotherapy. Serial evaluations at pretransplant, following return of bone marrow, and at predischarge were available for 34 patients. For the psychologic data, patients with hematologic disorders tended to be more distressed than breast cancer patients at baseline, but became less distressed over time. By contrast, breast cancer patients were relatively less distressed at baseline, demonstrated a significant increase in distress midtreatment, and returned to baseline levels at predischarge assessment. Scores on neuropsychologic measures that assessed higher order cognitive functioning generally worsened over time. CONCLUSION: The results suggest a differential response on psychologic measures when comparing patients with hematologic disorders with those with breast cancer. However, both groups demonstrated a general decline in performance on neuropsychologic measures over the course of treatment.

Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B.

PURPOSE: The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin. PATIENTS AND METHODS: Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17). RESULTS: No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001). CONCLUSION: Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.

Psychiatric status of patients with primary fibromyalgia, patients with rheumatoid arthritis, and subjects without pain: a blind comparison of DSM-III diagnoses.

OBJECTIVE: The major purpose of this study was to compare the frequency of the occurrence of DSM-III diagnoses in patients with primary fibromyalgia syndrome, patients with rheumatoid arthritis, and subjects without pain. METHOD: Thirty-five patients with primary fibromyalgia, 33 patients with rheumatoid arthritis, and 31 nonpatients without pain were blindly assessed for psychiatric diagnoses with the Psychiatric Diagnostic Interview. RESULTS: Data from this interview revealed no group differences in terms of lifetime history of any psychiatric disorders, including major depression, somatization disorder, or anxiety-based disorders. Analysis of the auxiliary symptoms of depression on the Psychiatric Diagnostic Interview revealed that the patients with fibromyalgia did not report a higher frequency of vegetative signs of depression. However, analysis of the somatization scale revealed an interaction between medical and psychiatric diagnoses: patients with primary fibromyalgia syndrome and a psychiatric history endorsed significantly more somatic symptoms than did patients with rheumatoid arthritis or subjects without pain, and fibromyalgia patients without a psychiatric history were no more likely to endorse somatic symptoms than were arthritis patients or subjects without pain. CONCLUSIONS: The Psychiatric Diagnostic Interview data failed to discriminate in any major way between primary fibromyalgia syndrome (a disorder with no known organic etiology) and rheumatoid arthritis (a disorder with a known organic etiology). Therefore, these data do not support a psychopathology model as a primary explanation of the symptoms of primary fibromyalgia syndrome.

Prevalence of mood disorders and utility of the PRIME-MD in patients undergoing radiation therapy.

PURPOSE: To validate a short, structured interview procedure that allows practicing oncologists to quickly and reliably identify mood disorders in their patients, and to estimate the prevalence and types of mood disorders in a radiation therapy patient setting, noting relationships between mood disorders and patient characteristics. METHODS: Consecutive, eligible adult patients from the practices of two radiation oncologists were administered the Primary Care Evaluation of Mental Disorders (PRIME-MD) by the treating physician. A subset of these patients was also evaluated with the SCID, administered by trained mental health care personnel. Agreement between the two instruments was examined using the kappa statistic. Prevalence of mood disorders was determined from the PRIME-MD. The significance of relationships between patient characteristics and mood disorders was examined by chi-square and ANOVA analysis, and subsequently by multivariate logistic regression analysis. RESULTS: One hundred twenty-two patients were studied. Fifty-three of these were administered the SCID. Agreement between the two instruments was very good (kappa = 0.70). A diagnosis of a depressive or anxiety disorder by the PRIME-MD was made in 59 of the 122 patients (48%, 95% confidence interval = 39%, 58%). Multivariate analysis showed that a diagnosis of a depressive mood disorder was significantly related to pain intensity and prior history of depression. CONCLUSION: We have demonstrated the validity and feasibility of the PRIME-MD administered by oncologists in making diagnoses of mood disorders. The prevalence of mood disorders in our set of patients undergoing a course of RT was nearly 50%. Future studies should describe the natural history of these disorders, and determine optimal intervention strategies.

Panel-based pain management in primary care. a pilot study.

Although pain is an extremely common symptom presenting to primary care physicians, it frequently is not optimally managed. The purpose of this feasibility study was to develop and pilot-test an efficient, rapid assessment and management approach for pain in busy community practices. The intervention utilized the Dartmouth COOP Clinical Improvement System (DCCIS) and a telephone-based, nurse-educator intervention. Patients from four primary care practices in rural New Hampshire and Vermont were screened by mail for the presence of persistent pain. Patients with mild to severe pain were randomized to either the usual care control group (n = 383) or the intervention group (n = 320). Patients who reported pain but no psychosocial problems received a summary of identified problems and targeted educational material via mail (DCCIS). Patients who reported pain and psychosocial problems received the DCCIS intervention and calls from a nurse-educator who provided pain self-management strategies and a problem-solving approach for psychosocial problems. Post-treatment evaluation revealed that patients in the intervention group scored significantly better on the Pain, Physical, Emotional, and Social subscales of the SF-36 and on the total score of the Functional Interference Scale, as compared to a usual care control group. Feasibility and acceptability of the approach were demonstrated; however, the conclusions based on analyses of the post-treatment outcomes were tempered by baseline imbalances across groups.

Knowledge and attitudes of health-care providers toward cancer pain management: a comparison of physicians, nurses, and pharmacists in the state of New Hampshire.

The knowledge and attitudes toward cancer pain management of physicians, nurses, and pharmacists in the state of New Hampshire were examined through the use of a statewide survey. Many of the providers who completed the survey, and thus indicated that they treated patients with cancer pain on a regular basis, were not pain or oncology specialists. Most of these providers were quite well informed about the fundamentals of cancer pain management. Approximately 90% of providers in all three groups were not concerned about addiction among cancer patients. Yet, there was a small percentage of providers who responded in less than optimal ways to items dealing with opioid pharmacology, pain assessment, and the importance of pain relief. Comparison of responses among provider groups indicated that nurses were the most knowledgeable and pharmacists the least knowledgeable about pain assessment. Physicians were the most knowledgeable regarding opioid pharmacology but seemed the least committed to providing optimal pain relief. Further analysis identified a small group of physicians that included a disproportionately high percentage of family practitioners and surgeons who consistently responded in less than optimal ways to items dealing with the importance of pain relief. The results of this study indicate a continuing need for broad-based educational programs in cancer pain management and for new initiatives focused on practitioners who see relatively few cancer patients and may have difficulty accessing traditional educational programs.

Dyspnea, anxiety, body consciousness, and quality of life in patients with lung cancer.

Dyspnea is a common symptom of lung cancer that can impact patient physical, social, and psychological well-being. Study goals were to evaluate quality of life (QOL) and dyspnea in patients with lung cancer and the relationships between QOL, dyspnea, trait anxiety, and body consciousness. Sociodemographic and cancer-related variables (stage, cell type, performance status) were evaluated. One hundred twenty outpatients with stage I-IV lung cancer participated in the study. Patients completed 5 questionnaires assessing QOL, dyspnea, trait anxiety, body consciousness, and pain. Eighty-seven percent of study participants experienced dyspnea. Patients with high dyspnea scores had lower QOL (P = 0.04). Dyspnea was worse in men than in women (P = 0.02), and there was a trend towards older patients reporting more severe dyspnea than younger patients (P = 0.06). There was no difference in dyspnea based on cancer stage, cell type, or performance status. Pain and anxiety scores were higher in patients with high dyspnea (P = 0.02, P = 0.03). Dyspnea was more severe in patients taking opioid analgesics when compared to non-opioids or no pain medications (P = 0.03). No significant association was found between dyspnea, anxiety, and private body consciousness.

Massage therapy for patients undergoing autologous bone marrow transplantation.

The purpose of the current study was to examine the impact of massage therapy on psychological, physical, and psychophysiological measures in patients undergoing autologous bone marrow transplantation (BMT). Patients scheduled to undergo BMT were randomly assigned to receive either (a) massage therapy, consisting of 20-minute sessions of shoulder, neck, head, and facial massage, or (b) standard treatment. Overall effects of massage therapy on anxiety, depression, and mood were assessed pretreatment, midtreatment, and prior to discharge using the State-Trait Anxiety Inventory, Beck Depression Inventory, and Brief Profile of Mood States, respectively. The immediate effects of massage were measured via the State Anxiety Inventory, Numerical Scales of Distress, Fatigue, Nausea, and Pain and indices of psychophysiological arousal (heart rate, blood pressure, and respiration rate), collected prior to and following patients' first, fifth, and final massage (on Days--7, midtreatment, and predischarge). Analysis of the data evaluating the immediate effects of massage showed that patients in the massage therapy group demonstrated significantly larger reductions in distress, fatigue, nausea, and State Anxiety than the standard treatment group at Day-7, in State Anxiety at midtreatment, and in fatigue at the predischarge assessment. The overall measures of psychological symptoms measured at pretreatment, midtreatment, and prior to discharge showed no overall group differences, although the massage group scored significantly lower on the State Anxiety Inventory than the standard care group at the midtreatment assessment. The two groups together showed significant declines through time on scores from the Profile of Mood States and State and Trait Anxiety Inventories.

Streamlining nutritional care for the physician's office.

OBJECTIVE: Nutritional care needs are overlooked in clinical practice. We review nutritional needs and describe an approach for improving nutritional care in clinical practice. DESIGN: Data from a controlled trial and several population cohorts. SETTING: Primary care practices and a population survey in New Hampshire and Vermont, USA. SUBJECTS: The controlled trial involved 1651 persons aged 70+years. The cohorts include information from 1879 persons aged 12+. INTERVENTION: All patients completed standard surveys which included information about nutritional needs. 22 practices participated in the trial. RESULTS: The higher the BMI, the less healthy the population. 15 30% of patients report problems or concerns with eating/weight and nutrition. Patients with problems or concerns are often bothered by other health and social problems. Patients who have productive interactions with clinicians have improved nutritional care and are more likely to report help with eating problems (68% vs 86%; Odds ratio 5.0 (95% CI: 0.9-27.0). CONCLUSIONS: Nutritional issues are common and complex. A productive provider-patient interaction can improve the nutritional care of patients. Essential elements for a productive interaction include an informed, educated patient and a provider (or clinical team) prepared to assess and manage the broad range of issues that are important to the patient. Technology facilitates necessary feedback between patient and provider.

Cancer-related pain--I. Prevalence in an outpatient setting as a function of stage of disease and type of cancer.

Cancer-related pain is a clinical problem of enormous significance that has received relatively little scientific study. Most reports of its prevalence and treatment have examined inpatient populations with varying degrees of regard for the stage of disease and the presence of non cancer-related sources of pain. In the present study, 208 consecutive ambulatory patients with cancer were evaluated. Nearly half (47.9%) reported no pain during the preceding week, 33.5% had pain directly referable to their cancer and 6.7% were suffering from pain related to therapy for their cancer. A small group (11%) had pain readily attributable to a source other than their cancer. Patients with metastatic disease, particularly those with bone metastases, reported cancer-related pain significantly more often than patients with local and regional disease (p less than 0.001). Patients with lymphoma reported the presence of cancer-related pain significantly less often than patients in all other diagnostic categories (p less than 0.001).

Cancer-related pain--II. Assessment with visual analogue scales.

As an attempt to develop an assessment methodology which is practical for use with severely ill cancer patients, Visual Analogue Scales (VAS) of pain, depression and anxiety were compared to standard measures of these variables in 29 outpatients and 11 inpatients suffering from cancer-related pain. Support for the validity of the VAS-Pain and VAS-Depression but not the VAS-Anxiety was found. These results demonstrate that the VAS-Pain and VAS-Depression provide a practical, valid method for assessing the sensory and affective components of cancer-related pain.

Private body consciousness, anxiety and pain symptom reports of chronic pain patients.

An information processing model of pain symptom perception and reporting predicts that individuals prone to high levels of attentional self-focus and negative affect will report more pain than individuals low in these characteristics. Past research on college student and medical patient samples has shown that individuals high in private body consciousness (PBC), or attentional self-focus and who report higher levels of anxiety report more pain symptoms than counterparts low in PBC and anxiety. The present study examined effects of PBC and anxiety on pain reports of individuals suffering chronic pain (N = 144). Pain patients suffering chronic headache, low back pain, rheumatoid arthritis and fibromyalgia were included in the sample. A non-pain control sample (N = 31) was also studied to examine potential differences between controls and pain patients. Results indicated that pain patients reporting high levels of PBC reported more pain, although the effects of anxiety on pain reports among pain patients was not significant. Controls did not differ from pain patients on PBC, nor did the 4 groups of pain patients differ on PBC, suggesting PBC is a dispositional variable. Implications for the importance of attentional self-focus in pain symptom reporting are discussed.

Formative evaluation of a multimedia program for patients about the side effects of cancer treatment.

Formative evaluation of multimedia programs can prevent costly and time-consuming revisions and result in more effective programs. Yet systematic formative evaluation is seldom conducted. This paper reviews the basic principles of formative evaluation and describes how we applied those principles to the formative evaluation of a multimedia program for patients about the side effects of cancer treatment. It discusses the challenges of developing multimedia programs for patients and provides guidance to other health professionals interested in developing programs on other topics.

Impact of aftercare arrangements on the maintenance of treatment success in abusive drinkers.

Aftercare to prevent relapse following alcohol treatment has not received adequate experimental investigation. The present study monitored alcohol intake of 50 patients following assignment to either an intensive aftercare recruitment procedure or regular clinic aftercare. The results indicated that those who received the intensive aftercare procedure showed delayed relapse. In addition, regardless of group assignment those who attended aftercare had significantly more success as measured by alcohol intake. The implications of these results for the design of treatment and aftercare programs are discussed.

Behavioral analysis and treatment of reflexive vomiting associated with visceral sensations: a case study of interoceptive conditioning?

Behavior analytic methods are applied to the conceptualization and treatment of a complex case of interoceptive classical conditioning. The subject exhibited a gagging and vomiting response to bladder and/or similar visceral sensations. A two-factor learning model of the problem led to a successful exposure and response prevention intervention, which was based on single-case experimental methodology. We discuss the possible relevance of this case in the context of the growing attention to interoceptive conditioning in behavioral problems, and comment upon the importance of behavior analytic principles and procedures to the behavioral clinician.