Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.

PURPOSE: To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue. RESULTS: The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity. CONCLUSION: This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.     

Is there a relationship between overweight and obesity and mental health problems in 4- to 5-year-old Australian children?

OBJECTIVE: To investigate the relationship between overweight and obesity, and mental health problems in Australian 4- to 5-year-old children. METHODS: The study used data from wave 1 (2004) of the Longitudinal Study of Australian Children (LSAC). The participants were 4983 4- to 5-year-old children (2537 boys and 2446 girls) with a mean age of 56.9 months (standard deviation 2.6 months; range 51-67 months). Children were classified as nonoverweight, overweight, and obese on the basis of International Obesity Task Force definitions. Mental health problems were assessed by the Strengths and Difficulties Questionnaire (SDQ) completed by parents and teachers. RESULTS: Although obese 4- to 5-year-old boys had more mental health problems than nonoverweight boys, differences between the groups were small and substantially reduced when analyses controlled for children's sociodemographic characteristics. Parents reported that overweight/obese girls had more peer problems, whereas teachers reported they had more conduct problems. Children in all weight groups had mean scores within the normal range of scores on all the SDQ subscales. CONCLUSIONS: Differences in rates of mental health problems experienced by young children of different weight status appear relatively small. Higher rates of mental health problems experienced by more obese boys may reflect differences in their sociodemographic characteristics rather than their weight status per se. Policies that reduce the number of young children living in poverty or experiencing other adverse social circumstances have the potential to reduce rates of mental health problems experienced by older children with overweight/obesity.     

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.     

Feasibility and acceptability of a motivational interviewing breastfeeding peer support intervention

An uncontrolled study with process evaluation was conducted in three U.K. community maternity sites to establish the feasibility and acceptability of delivering a novel breastfeeding peer‐support intervention informed by motivational interviewing (MI; Mam‐Kind). Peer‐supporters were trained to deliver the Mam‐Kind intervention that provided intensive one‐to‐one peer‐support, including (a) antenatal contact, (b) face‐to‐face contact within 48 hr of birth, (c) proactive (peer‐supporter led) alternate day contact for 2 weeks after birth, and (d) mother‐led contact for a further 6 weeks. Peer‐supporters completed structured diaries and audio‐recorded face‐to‐face sessions with mothers. Semistructured interviews were conducted with a purposive sample of mothers, health professionals, and all peer‐supporters. Interview data were analysed thematically to assess intervention acceptability. Audio‐recorded peer‐support sessions were assessed for intervention fidelity and the use of MI techniques, using the MITI 4.2 tool. Eight peer‐supporters delivered the Mam‐Kind intervention to 70 mothers in three National Health Service maternity services. Qualitative interviews with mothers (n = 28), peer‐supporters (n = 8), and health professionals (n = 12) indicated that the intervention was acceptable, and health professionals felt it could be integrated with existing services. There was high fidelity to intervention content; 93% of intervention objectives were met during sessions. However, peer‐supporters reported difficulties in adapting from an expert‐by‐experience role to a collaborative role. We have established the feasibility and acceptability of providing breastfeeding peer‐support using a MI‐informed approach. Refinement of the intervention is needed to further develop peer‐supporters' skills in providing mother‐centred support. The refined intervention should be tested for effectiveness in a randomised controlled trial.     

The space-time profiles of sleep spindles and their coordination with slow oscillations on the electrode manifold

Sleep spindles are important for sleep quality and cognitive functions, with their coordination with slow oscillations (SOs) potentially organizing cross-region reactivation of memory traces. Here, we describe the organization of spindles on the electrode manifold and their relation to SOs. We analyzed the sleep night EEG of 34 subjects and detected spindles and SOs separately at each electrode. We compared spindle properties (frequency, duration, and amplitude) in slow wave sleep (SWS) and Stage 2 sleep (S2); and in spindles that coordinate with SOs or are uncoupled. We identified different topographical spindle types using clustering analysis that grouped together spindles co-detected across electrodes within a short delay (±300 ms). We then analyzed the properties of spindles of each type, and coordination to SOs. We found that SWS spindles are shorter than S2 spindles, and spindles at frontal electrodes have higher frequencies in S2 compared to SWS. Furthermore, S2 spindles closely following an SO (about 10% of all spindles) show faster frequency, shorter duration, and larger amplitude than uncoupled ones. Clustering identified Global, Local, Posterior, Frontal-Right and Left spindle types. At centro-parietal locations, Posterior spindles show faster frequencies compared to other types. Furthermore, the infrequent SO-spindle complexes are preferentially recruiting Global SO waves coupled with fast Posterior spindles. Our results suggest a non-uniform participation of spindles to complexes, especially evident in S2. This suggests the possibility that different mechanisms could initiate an SO-spindle complex compared to SOs and spindles separately. This has implications for understanding the role of SOs-spindle complexes in memory reactivation.     

White patients’ physical responses to healthcare treatments are influenced by provider race and gender

The healthcare workforce in the United States is becoming increasingly diverse, gradually shifting society away from the historical overrepresentation of White men among physicians. However, given the long-standing underrepresentation of people of color and women in the medical field, patients may still associate the concept of doctors with White men and may be physiologically less responsive to treatment administered by providers from other backgrounds. To investigate this, we varied the race and gender of the provider from which White patients received identical treatment for allergic reactions and measured patients’ improvement in response to this treatment, thus isolating how a provider’s demographic characteristics shape physical responses to healthcare. A total of 187 White patients experiencing a laboratory-induced allergic reaction interacted with a healthcare provider who applied a treatment cream and told them it would relieve their allergic reaction. Unbeknownst to the patients, the cream was inert (an unscented lotion) and interactions were completely standardized except for the provider’s race and gender. Patients were randomly assigned to interact with a provider who was a man or a woman and Asian, Black, or White. A fully blinded research assistant measured the change in the size of patients’ allergic reaction after cream administration. Results indicated that White patients showed a weaker response to the standardized treatment over time when it was administered by women or Black providers. We explore several potential explanations for these varied physiological treatment responses and discuss the implications of problematic race and gender dynamics that can endure “under the skin,” even for those who aim to be bias free.

The face of medicine is changing. Women and people of color make up an increasing percentage of health care providers (1–3). In 2017, for the first time in history, women were the majority of accepted medical school applicants in the United States and the number of non-White accepted applicants rose to above 50%. Here, we ask whether this recent demographic shift in the race and gender of doctors is also shifting long-held, societally pervasive notions of what a doctor “looks like.”Despite the increasing diversity of the medical field, for most people in most contexts, the association between “doctor” and “White man” is still likely strong and pervasive. This is hardly surprising. For most of medical history in North America, the majority of physicians fit this profile (see Fig. 1 A and B), and even now the majority of practicing physicians are still men and nearly half are White (see Fig. 1 C and D). Consequently, the emerging links between “Doctor and Woman” and between “Doctor and Black person,” for example, are likely weak. Moreover, to the extent that those associations exist, they are likely to have to compete for attention with an array of strong, frequent, and negative associations that undermine the links between women and competence and African Americans and competence (4–6).Open in a separate windowFig. 1.The change in the representation of women (A) and people color (B) in the number of accepted applicants to US medical schools, as well as the current representation of professionally active women physicians (C) and physicians of color (D). (A and B) From the Association of American Medical Colleges (AAMC). (C) From the Henry J. Kaiser Family Foundation. (D) From 2013 from the Association of American Medical Colleges (AAMC). AAMC data on race/ethnicity were not available for 2013 or 2014, hence explaining the gaps in the graph around these years in B.In patient–provider interactions, as in every social encounter, people bring with them a set of learned associations about social groups that have been formed by their various life experiences (e.g., personal interactions, media exposure) (6–12). Mirroring the historical representation of doctors in actual medical practice, representations of doctors in popular media have overwhelmingly been as White men (13–15). Patients who have learned this societally pervasive “Doctor = White man” association through their actual encounters with physicians as well as through movies, television, books, and advertising may respond less positively to care from Black and women providers. These associations may exist at an implicit level even in the context of positive explicit attitudes toward Black doctors and women doctors (16, 17), and they are potentially powerful, influencing the course of medical care. Also, while it is clear from past research that being a target of bias can be harmful to health (e.g., people who face race-based discrimination face adverse physical and mental health consequences) (18), it is unclear whether viewing another social group in light of societally pervasive associations (e.g., about doctors on the basis of gender and race) can be harmful to the health of the perceiver.Here, we focus on how the race and gender of doctors may impact patients’ responses to the expectations doctors set about medical treatment. Previous research shows that a provider’s expressed expectations for a medical treatment (i.e., that it will benefit patients) can improve patient engagement, adherence, and physiological responses to treatment (19–25). Based on these findings, we anticipate that patients who interact with a doctor whose personal characteristics (e.g., race, gender) do not conform to dominant societal representations of what a doctor looks like may be less responsive to such expectations. We hypothesize that patients may be less responsive to the exact same medical treatment when the doctor who sets expectations that this treatment will be beneficial is not a White man.This hypothesis draws on a large and growing body of research suggesting that the total effect of a healthcare treatment depends on the social context in which that treatment takes place (25–29). The realization that the social context can influence treatment and medical outcomes is bolstered by a large body of research on the placebo effect (26). Although people may sometimes assume that actual pharmaceutical properties of a medication or treatment are solely responsible for its total benefit, placebo paradigms show that the total effect of treatment is in fact a combined product of the drug and their medical properties (e.g., acetaminophen, antihistamines), the body’s natural healing abilities (e.g., endogenous opioids and antihistamines), and the psychological and social context (e.g., what a patient believes about treatment and the qualities of the person who administers the treatment) (SI Appendix, Fig. S1). For example, past research suggests that a physician’s characteristics, such as their projected warmth and competence, influences how much a patient improves in response to treatment. In one recent study (22), the researchers independently manipulated whether a provider acted more or less warm, and more or less competent, toward a patient during an allergy skin prick test that induced a mild allergic reaction. The provider set positive expectations about a placebo cream (i.e., unscented hand lotion) placed on the reaction, informing patients that this cream was an antihistamine that would reduce the reaction. When the provider was both warm and competent, patients showed a stronger physiological response to the placebo treatment over time; their allergic reaction decreased the most rapidly in size, in response to the positive expectations that the provider had set. Thus, aspects of social interactions with providers can influence the degree to which the positive expectations that a provider sets about treatment ultimately influence physiological treatment response.As in most social interactions in the United States, race and gender are likely salient aspects of the social context in patient–provider interactions (30, 31, 32). Previous research has found, for example, that patient race can influence the quality of care received from doctors in myriad ways (33–36). Here, we focus on provider race and provider gender as features of the social context that can influence patients’ response to treatment. Specifically, we ask the following: will White patients exhibit a weaker physiological response to the expectations set about treatment by doctors who are not White and men?     

Feasibility of Spotlight Consultations Tool in Routine Care: Real-World Evidence

Background:Burnout in people with diabetes and healthcare professionals (HCPs) is at an all-time high. Spotlight AQ, a novel “smart” adaptive patient questionnaire, is designed to improve consultations by rapidly identifying patient priorities and presenting these in the context of best-practice care pathways to aid consultations. We aimed to determine Spotlight AQ’s feasibility in routine care.Materials and Methods:The Spotlight prototype tool was trialed at three centers: two UK primary care centers and one US specialist center (June-September 2020). Participants with type 1 (T1D) or type 2 diabetes (T2D) completed the questionnaire prior to their routine consultations. Results were immediately available and formed the basis of the clinical discussion and decision-making within the clinic visit.Results:A convenience sample of 49 adults took part, n=31 T1D, (n=18 female); and n=18 T2D (n=10 male, n=4 female, n=4 gender unreported). Each identified two priority concerns. “Psychological burden of diabetes” was the most common priority concern (T1D n = 27, 87.1%) followed by “gaining more skills about particular aspects of diabetes” (T1D n=19, 61.3%), “improving support around me” (n=8, 25.8%) and “diabetes-related treatment issues” (n=8, 25.8%). Burden of diabetes was widespread as was lack of confidence around self-management. Similarly, psychological burden of diabetes was the primary concern for participants with T2D (n=18,100%) followed by “gaining more skills about aspects of diabetes” (n=7, 38.9%), “improving support around me” (n=7, 38.9%) and “diabetes-related treatment issues” (n=4; 22.2%).Conclusions:Spotlight AQ is acceptable and feasible for use in routine care. Gaining more skills and addressing the psychological burden of diabetes are high-priority areas that must be addressed to reduce high levels of distress.