The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort.

BACKGROUND: 5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are not well described. Through using a well-characterised cohort of 5-year survivors of the most common childhood cancers, we evaluated specific health-related causes of late mortality and excess deaths compared with the general US population and identified targets to reduce future risk. METHODS: In this multi-institutional, hospital-based, retrospective cohort study, late mortality (death ≥5 years from diagnosis) and specific causes of death were evaluated in 34 230 5-year survivors of childhood cancer diagnosed at an age younger than 21 years from 1970 to 1999 at 31 institutions in the USA and Canada; median follow-up from diagnosis was 29 years (range 5-48) in the Childhood Cancer Survivor Study. Demographic, self-reported modifiable lifestyle (ie, smoking, alcohol, physical activity, and BMI) and cardiovascular risk factors (ie, hypertension, diabetes, and dyslipidaemia) associated with health-related mortality (which excludes death from primary cancer and external causes and includes death from late effects of cancer therapy) were evaluated. FINDINGS: 40-year cumulative all-cause mortality was 23·3% (95% CI 22·7-24·0), with 3061 (51·2%) of 5916 deaths from health-related causes. Survivors 40 years or more from diagnosis experienced 131 excess health-related deaths per 10 000 person-years (95% CI 111-163), including those due to the top three causes of health-related death in the general population: cancer (absolute excess risk per 10 000 person-years 54, 95% CI 41-68), heart disease (27, 18-38), and cerebrovascular disease (10, 5-17). Healthy lifestyle and absence of hypertension and diabetes were each associated with a 20-30% reduction in health-related mortality independent of other factors (all p values ≤0·002). INTERPRETATION: Survivors of childhood cancer are at excess risk of late mortality even 40 years from diagnosis, due to many of the leading causes of death in the US population. Modifiable lifestyle and cardiovascular risk factors associated with reduced risk for late mortality should be part of future interventions. FUNDING: US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Risk of increased mortality in underweight survivors: A brief report from the Childhood Cancer Survivor Study.

BACKGROUND: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown. OBJECTIVE: To determine whether underweight status increases the risk of mortality. PROCEDURE: Cohort study: Marginal models with generalized estimating equations to evaluate the associations between body mass index (BMI), serious or life-threatening chronic conditions, and death in the setting of long-term follow-up questionnaires and National Death Index search. PARTICIPANTS: Childhood cancer five-year survivors diagnosed during 1970-1986 in the Childhood Cancer Survivor Study Exposure: Underweight status, defined as body mass index (BMI) < 18.5 kg/m2 compared with ideal body weight. Based on available literature on body weight and mortality from the general population, ideal body weight was defined as BMI 22.0-24.9 kg/m2. MAIN OUTCOMES: Overall mortality and cancer-specific mortality. RESULTS: Of 9454 survivors (median age 35 years old (range, 17-58), an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline or follow-up questionnaire. Of 184 deaths, 29 were among underweight survivors. Underweight status was more common among females (9.1% vs. 4.5%, p < .01) and participants with younger age at diagnosis (8.2% for < 5 years vs. 6.1% for ≥5 years, p < .01), lower household income (8.9% for < $20,000 vs. 6.0% for ≥ $20,000, p < .01), or a history of serious chronic condition (p = .05). After adjustment for these factors, in addition to prior smoking and a history of radiation therapy, the risk of all-cause mortality within two years of BMI report was increased (OR 2.85; 95% CI: 1.63-4.97; p < .01) for underweight survivors, compared with ideal-weight survivors. CONCLUSIONS: Childhood cancer survivors who are underweight are at increased risk for late mortality that appears unrelated to smoking status, recognized chronic disease, or subsequent malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

Neurostimulation for childhood epilepsy.

The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the developing brain. In this review, we discuss the available evidence for neurostimulation for childhood epilepsy. Vagus nerve stimulation (VNS) is the most studied neurostimulation modality in children. Based on mostly retrospective, open-label studies, we can conclude that VNS has a similar safety and efficacy profile in children compared to adults. Although there is little available evidence for deep brain stimulation (DBS) and responsive neurostimulation (RNS) in children, both DBS and RNS show promise in reducing seizure frequency with few complications. The implementation of non-invasive techniques with a more appealing safety profile has gained interest. Small randomized control trials and open-label studies have investigated transcranial direct current simulation for childhood epilepsy, demonstrating promising but inconsistent findings.

Investigating the Working Mechanism of Transcranial Direct Current Stimulation.

BACKGROUND: Transcranial direct current stimulation (tDCS) is used to modulate neuronal activity, but the exact mechanism of action (MOA) is unclear. This study investigates tDCS-induced modulation of the corticospinal excitability and the underlying MOA. By anesthetizing the scalp before applying tDCS and by stimulating the cheeks, we investigated whether stimulation of peripheral and/or cranial nerves contributes to the effects of tDCS on corticospinal excitability. MATERIALS AND METHODS: In a randomized cross-over study, four experimental conditions with anodal direct current stimulation were compared in 19 healthy volunteers: 1) tDCS over the motor cortex (tDCS-MI), 2) tDCS over the motor cortex with a locally applied topical anesthetic (TA) on the scalp (tDCS-MI + TA), 3) DCS over the cheek region (DCS-C), and 4) sham tDCS over the motor cortex(sham). tDCS was applied for 20 minutes at 1 mA. Motor evoked potentials (MEPs) were measured before tDCS and immediately, 15, 30, 45, and 60 minutes after tDCS. A questionnaire was used to assess the tolerability of tDCS. RESULTS: A significant MEP amplitude increase compared with baseline was found 30 minutes after tDCS-MI, an effect still observed 60 minutes later; no time∗condition interaction effect was detected. In the other three conditions (tDCS-MI + TA, DCS-C, sham), no significant MEP modulation was found. The questionnaire indicated that side effects are significantly lower when the local anesthetic was applied before stimulation than in the other three conditions. CONCLUSIONS: The significant MEP amplitude increase observed from 30 minutes on after tDCS-MI supports the modulatory effect of tDCS on corticospinal neurotransmission. This effect lasted one hour after stimulation. The absence of a significant modulation when a local anesthetic was applied suggests that effects of tDCS are not solely established through direct cortical stimulation but that stimulation of peripheral and/or cranial nerves also might contribute to tDCS-induced modulation.

Childhood Cancer Survivors' Reported Late Effects, Motivations for Seeking Survivorship Care, and Patterns of Attendance.

BACKGROUND: Childhood cancer survivors are vulnerable to long-term treatment-related health conditions, which can lead to poor quality of life. Little data exist on the overall health of long-term Australian and New Zealand childhood cancer survivors or on survivors' motivations for attending survivorship clinics. METHODS: This study administers a cross-sectional questionnaire to long-term survivors ≥5 years from their primary diagnosis. We compared participant-reported number of late effects by a cancer diagnosis, and identified clinical (eg, treatment) and demographic (eg, age) factors that were associated with late effects burden and engagement in cancer survivorship care. RESULTS: A total of 634 participants completed questionnaires (48% male, mean age = 21.7 years). Most participants (79%) reported at least one cancer-related late effect, most commonly fatigue (40%) and memory/learning difficulties (34%). Brain tumor survivors reported a higher total number of late effects than survivors with other diagnoses (mean = 5.7 vs. 3.2, P < .001). Participants' most commonly reported motivators for engaging in care were to understand problems that may occur later in life because of their cancer and/or treatment (98.5%) and to get reassurance about one's health (97.4%). The proportion of survivors endorsing each motivating factor was similar across cancer diagnoses, with the exception of learning more about insurance and pensions (highest in brain tumor survivors = 80%). In multivariable analyses, survivors were more likely to report being engaged in survivorship care if they were younger (P < .001), less time had elapsed since their diagnosis (P < .001), or they reported a higher number of motivating factors (P = .016). CONCLUSION: Survivors report a range of health problems decades after treatment completion. Understanding the burden of late effects, and motivators for seeking survivorship care to manage these health problems, is important for ensuring that tailored interventions or services are available to meet the needs of this growing population and to design effective models of survivorship care.

Clinic reported facilitators and barriers to pediatric cancer survivor care delivery among survivorship clinics: A fishbone analysis.

BACKGROUND: Childhood cancer survivors need regular, long-term survivor care. The Children's Oncology Group (COG) recommends that pediatric patients receive ongoing, evidence-based surveillance for late effects, beginning 2 years after the completion of cancer therapy. However, at least a third of survivors are not engaging in long-term survivorship care. This study assessed facilitators and barriers to follow-up survivorship care through the perspectives of pediatric cancer survivor clinic representatives. METHODS: As part of a hybrid implementation-effectiveness trial, a representative from 12 participating pediatric cancer survivor clinics completed a survey about site characteristics and a semi-structured interview on facilitators and barriers to survivor care delivery at their institution. Interviews were grounded in the socio-ecological model (SEM) framework and utilized a fishbone diagram to understand what facilitates and impedes survivor care. We ran descriptive statistics and conducted thematic analyses of the interview transcripts to create two meta-fishbone diagrams. RESULTS: All participating clinics (N = 12) have existed for at least 5 years (mean = 15, median = 13, range = 3-31), and half (n = 6, 50%) reported seeing more than 300 survivors annually. In the fishbone diagram, the top facilitators were in the SEM domain of organization, specifically with familiar staff (n = 12, 100%), resource utilization (n = 11, 92%), dedicated survivorship staff (n = 10, 83%), and clinic processes (n = 10, 83%). Common barriers were across the domains of organization, community, and policy, which included distance/transportation to the clinic (n = 12, 100%), technology limits (n = 11, 92%), scheduling issues (n = 11, 92%), and insufficient funding/insurance (n = 11, 92%). CONCLUSION: Clinic staff and provider perceptions are instrumental in understanding multilevel contextual issues related to survivor care delivery for pediatric cancer survivor clinics. Future research can aid in developing education, processes, and services to promote cancer survivor follow-up care.

Influenza Vaccination Receipt in Pediatric Patients With Cancer or Sickle Cell Disease.

BACKGROUND: Influenza causes greater morbidity in children with cancer or sickle cell disease (SCD). Literature on influenza vaccination receipt for these populations is limited in low-vaccination states. Outpatient interventions improve vaccine receipt but isolated inpatient interventions remain unstudied. PROCEDURE: We reviewed influenza vaccine receipt of children with cancer or SCD treated at Children's Healthcare of Atlanta during three influenza seasons. We implemented a clinical decision support intervention during an influenza season and compared influenza vaccine receipt preintervention and postintervention among admitted children. RESULTS: The oncology cohort (N=1548, 60% to 62%) and the SCD cohort (N=2549, 61% to 65%) had similar-to-higher vaccination receipt to the United States (58% to 64%, P =0.01 to 0.79) and Georgia (51% to 56%, P <0.01). The intervention did not significantly improve vaccination receipt for admitted children with cancer (40% vs. 56%, P =0.05 to 0.88) or SCD (44% vs. 56%, P =0.01). Regression modeling also found no significant increase in vaccine receipt (hematologic malignancy: 0.8 [0.73 to 0.98], solid tumor: 0.9 [0.80 to 1.90], central nervous system tumor: 0.9 [0.71 to 1.14], SCD: 0.9 [0.85 to 0.99]). CONCLUSIONS: Children with cancer and SCD have similar-to-greater influenza vaccination receipt compared with Georgia and the United States. An inpatient intervention did not significantly improve influenza vaccine receipt in these patient cohorts. Future studies are needed to identify alternative approaches to improving vaccine receipt in these cohorts.

Change in carbohydrate intake one year after Roux-en-Y gastric bypass: A prospective study.

Background and objectives: To investigate the effect of carbohydrate intake before laparoscopic Roux-en-Y gastric bypass (LRYGB) on body weight, body composition and glycaemic status after surgery. Methods: In a tertiary centre cohort study, dietary habits, body composition and glycaemic status were evaluated before and 3, 6 and 12 months after LRYGB. Detailed dietary food records were processed by specialized dietitians on the basis of a standard protocol. The study population was subdivided according to relative carbohydrate intake before surgery. Results: Before surgery, 30 patients had a moderate relative carbohydrate intake (26%-45%, M-CHO), a mean body mass index (BMI) of 40.4 ± 3.9 kg/m² and a mean glycated haemoglobin A1c (A1C) of 6.5 ± 1.2% compared to 20 patients with a high relative carbohydrate intake (> 45%, H-CHO), mean BMI of 40.9 ± 3.7 kg/m² (non-significant, NS) and a mean A1C of 6.2% (NS). One year after surgery, body weight, body composition and glycaemic status were similar in the M-CHO (n = 25) and H-CHO groups (n = 16), despite less caloric intake in the H-CHO group (1317 ± 285 g vs. 1646 ± 345 g in M-CHO, p < 0.01). Their relative carbohydrate intake converged to 46% in both groups, but the H-CHO group reduced the absolute total carbohydrate consumption more than the M-CHO group (190 ± 50 g in M-CHO vs. 153 ± 39 g in H-CHO, p < 0.05), and this was especially pronounced for the mono- and disaccharides (86 ± 30 g in M-CHO vs. 65 ± 27 g in H-CHO, p < 0.05). Conclusion: A high relative carbohydrate intake before LRYGB, did not influence the change in body composition or diabetes status after surgery, despite a significantly lower total energy intake and less mono- and disaccharide consumption after surgery.

Investigating the Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Males.

OBJECTIVES: As a potential treatment for epilepsy, transcutaneous auricular vagus nerve stimulation (taVNS) has yielded inconsistent results. Combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) can be used to investigate the effect of interventions on cortical excitability by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of taVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms. MATERIALS AND METHODS: In this prospective single-blind cross-over study, 15 healthy male subjects underwent active and sham taVNS for 60 min, using a maximum tolerated stimulation current. Single and paired pulse TMS was delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention. MEP statistical analysis was conducted with a two-way repeated measures ANOVA. TEPs were analyzed with a cluster-based permutation analysis. Linear regression analysis was implemented to investigate an association with stimulation current. RESULTS: MEP and TEP measurements were not affected by taVNS in this study. An association was found between taVNS stimulation current and MEP outcome measures indicating a decrease in cortical excitability in participants who tolerated higher taVNS currents. A subanalysis of participants (n = 8) who tolerated a taVNS current ≥2.5 mA showed a significant increase in the resting motor threshold, decrease in MEP amplitude and modulation of the P60 and P180 TEP components. CONCLUSIONS: taVNS did not affect cortical excitability measurements in the overall population in this study. However, taVNS has the potential to modulate specific markers of cortical excitability in participants who tolerate higher stimulation levels. These findings indicate the need for adequate stimulation protocols based on the recording of objective outcome parameters.

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation.

BACKGROUND: Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings. MATERIALS AND METHODS: A total of 17 of 25 patients underwent LMEP recordings at initiation of therapy (acute group); 15 of 25 patients after one year of VNS (chronic group); and 7 of 25 patients were tested at both time points (acute + chronic group). VNS-induced LMEPs were recorded following different pulse widths and output currents using six surface laryngeal EMG electrodes to calculate input/output curves and estimate LMEP latency, threshold current for minimal (Ithreshold), half-maximal (I50), and 95% of maximal (I95) response induction and amplitude of maximal response (Vmax). These were compared with the acute + chronic group and between responders and nonresponders in the acute and chronic group. RESULTS: VNS-induced LMEPs were present in all patients. Ithreshold and I95 values ranged from 0.25 to 1.00 mA and from 0.42 to 1.77 mA, respectively. Estimated mean LMEP latencies were 10 ± 0.1 milliseconds. No significant differences between responders and nonresponders were observed. In the acute + chronic group, Ithreshold values remained stable over time. However, at the individual level in this group, Vmax was lower in all patients after one year compared with baseline. CONCLUSIONS: Noninvasive VNS-induced LMEP recording is feasible both at initiation of VNS therapy and after one year. Low output currents (0.25-1.00 mA) may be sufficient to activate vagal Aα-motor fibers. Maximal LMEP amplitudes seemed to decrease after chronic VNS therapy in patients.

Substance use, substance use disorders, and treatment in adolescent and young adult cancer survivors-Results from a national survey.

BACKGROUND: Substance use can exacerbate cancer-related morbidity and mortality in adolescent/young adult (AYA) cancer survivors and place them at increased risk for adverse health outcomes. The objective of this study was to assess substance use, misuse, and substance use disorders [SUDs], as well as receipt of treatment for SUDs, among AYA cancer survivors. METHODS: The authors used data from the National Survey of Drug Use and Health (2015-2018) to identify a nationally representative sample of AYAs aged 12 to 34 years. Outcomes assessed past-year tobacco, alcohol, marijuana, and illicit drug use; misuse of prescription opioids; SUDs; and SUD treatment. Multiple logistic regression was estimated to compare outcomes between 832 AYAs who reported a cancer history (survivors) and 140,826 AYAs who did not, adjusting sequentially for sociodemographic characteristics and health status. RESULTS: In regressions adjusting for sociodemographic characteristics, survivors were more likely than a noncancer comparison group of peers to use alcohol (6% relative increase; P = .048) and illicit drugs (34% relative increase; P = .012), to misuse prescription opioids (59% relative increase; P < .001), and to have a marijuana (67% relative increase; P = .011), illicit drug (77% relative increase; P < .001), or prescription opioid (67% relative increase; P = .048) SUD. When further adjusting for health status, survivors were still 41% more likely (P < .001) to misuse prescription opioids than noncancer peers. Among those with SUDs, survivors were more likely than peers to receive treatment (unadjusted, 21.5% vs 8.0%; adjusted, P < .05). CONCLUSIONS: AYA survivors were as likely as or more likely than noncancer peers to report substance use problems. These findings underscore the importance of interventions to reduce substance use and improve SUD treatment among AYA cancer survivors. LAY SUMMARY: The authors assessed substance use, misuse, and substance use disorders, as well as the receipt of treatment for substance use disorders, among adolescent and young adult (AYA) cancer survivors. In a nationally representative AYA sample, cancer survivors, despite their increased risk for morbidity and early mortality, were as likely as or more likely than peers without cancer to experience substance use problems. In particular, survivors had a significantly higher rate of prescription opioid misuse than peers. However, only 1 in 5 AYA survivors who experienced substance use disorders received treatment. These findings underscore the importance of interventions toward reducing substance use and improving access to treatment among AYA survivors.

National estimates of mental health service use and unmet needs among adult cancer survivors.

BACKGROUND: Cancer survivors are at elevated risk for developing mental health (MH) disorders. This study assessed MH service use and unmet service needs among a nationally representative sample of cancer survivors. METHODS: Respondents aged 18 to 64 years were identified from the 2015-2018 National Survey of Drug Use and Health data. Outcomes assessed past-year MH service use and self-reported unmet MH needs. Outcomes were compared between respondents who reported a cancer history (survivors) and those who did not (controls), descriptively and in adjusted analyses controlling for sociodemographic factors and health status. Analyses were stratified by age groups (18-34, 35-49, and 50-64 years). RESULTS: Comparing 3540 survivors with 149,843 controls, within each age group, a higher proportion of survivors than controls received any MH service (P values < .05); this difference persisted among those aged 35 to 49 years (P = .004) in fully adjusted models. Moreover, a higher proportion of survivors than controls reported an unmet need for MH care; this difference was larger among young adults aged 18 to 34 years (20.8% vs 9.0%; P < .001) than those aged 35 to 49 years (9.4% vs 5.3%; P < .001) and 50 to 64 years (4.8% vs 3.4%; P = .029). In fully adjusted models, the survivor-control difference in self-reported unmet MH needs persisted among young adults (24% relative increase; P = .023). Among cancer survivors, young adult survivors had the highest likelihood of reporting unmet MH needs. CONCLUSIONS: This nationally representative study found an increased perception of unmet needs for MH care among cancer survivors, particularly among young adult survivors, compared with the general population without cancer.

Patterns of surveillance for late effects of BCR-ABL tyrosine kinase inhibitors in survivors of pediatric Philadelphia chromosome positive leukemias.

BACKGROUND: Targeted anticancer therapies such as BCR-ABL tyrosine kinase inhibitors (TKIs) have improved outcomes for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, little is known about long-term risks of TKIs in children. Exposure-based survivorship guidelines do not include TKIs, thus surveillance practices may be variable. METHODS: We retrospectively examined surveillance for cardiac and endocrine late effects in children receiving TKIs for Ph + leukemias, diagnosed at < 21 years between 2000 and 2018. Frequency of echocardiogram (ECHO), electrocardiogram (EKG), thyroid stimulating hormone (TSH), dual-energy x-ray absorptiometry (DXA), and bone age testing were abstracted. Descriptive statistics were stratified by leukemia type. RESULTS: 66 patients (CML n = 44; Ph + ALL n = 22) met inclusion criteria. Among patients with CML, ≥1 evaluation was done: ECHO (50.0%), EKG (48.8%), TSH (43.9%), DXA (2.6%), bone age (7.4%). Among patients with Ph + ALL, ≥1 evaluation was done: ECHO (86.4%), EKG (68.2%), TSH (59.1%), DXA (63.6%), bone age (44.4%). Over a median 6.3 and 5.7 years of observation, respectively, 2% of patients with CML and 57% with Ph + ALL attended a survivorship clinic. CONCLUSIONS: Despite common exposure to TKIs in survivors of Ph + leukemias, patterns of surveillance for late effects differed in CML and Ph + ALL, with the latter receiving more surveillance likely due to concomitant chemotherapy exposures. Targeted therapies such as TKIs are revolutionizing cancer treatment, but surveillance for late effects and referral to survivorship clinics are variable despite the chronicity of exposure. Evidence based guidelines and longer follow-up are needed.

Using formative evaluation to plan for electronic psychosocial screening in pediatric oncology.

OBJECTIVE: To demonstrate how formative research methods can be used to plan for implementation of evidence-based psychosocial screening in pediatric oncology. METHODS: Multidisciplinary pediatric oncology professionals participated in focus groups to adapt the distress thermometer for electronic administration and develop health systems processes to promote psychosocial screening in the pediatric oncology outpatient clinic setting. Seven 1-hour focus groups were conducted using a structured guide based on the reach, efficacy, adoption, implementation, and maintenance framework and transcribed verbatim. Two independent raters coded transcripts using a quasi-deductive approach with high inter-coder reliability (Cohen kappa >0.80). RESULTS: Participants' (N = 44) responses were used to identify overarching topics related to the adoption, implementation, and maintenance of electronic screening (e-screening) including: barriers to meeting families' psychosocial needs, identification of champions, suggestions to adapt the proposed e-screening program, perceived barriers to e-screening, and potential impact of carrying out e-screening. Following review of qualitative data, we employed specific implementation strategies to promote adoption, implementation, and maintenance of an e-screening program. CONCLUSIONS: Perceived barriers to the implementation of psychosocial screening remain substantial, yet enthusiasm for using electronic health records (EHRs) technology to help meet patient needs through regular assessment was evident among pediatric oncology professionals. Electronic administration of screening and integration of results into the EHR in real time were identified as critical needs to overcome barriers to e-screening. Formative research including qualitative data from stakeholders can be used to tailor implementation strategies to successfully support the adoption, implementation, and maintenance of e-screening programs in pediatric oncology.

Features Associated With Weight Loss and Growth Stunting for Young Children During Cancer Therapy.

Features associated with malnutrition are poorly elucidated in pediatric cancer care. We aimed to better understand characteristics associated with weight-for-height (WHZ) and height-for-age (HAZ) changes for infants and young children during cancer treatment. This retrospective study included 434 patients diagnosed <3 years old from 2007 to 2015 at a large pediatric cancer center. Patients starting treatment outside our center, those with relapsed or secondary malignancies, or with inaccurate information were excluded. Abstracted weights and heights for a 24-month period after treatment initiation were converted to sex-specific and age-specific z scores. Although not statistically different at baseline, patients with hematologic malignancies gained weight over time, while other tumor types did not. Higher treatment intensity and younger age at diagnosis increased odds of clinically significant weight loss. Older children had higher HAZ at diagnosis and HAZ also significantly decreased over time for all examined risk factors, which is distinctly different from patterns in WHZ over time. In conclusion, WHZ and HAZ are affected differently by cancer treatment in infants and young children. We identify key risk factors for weight loss and growth stunting which will be necessary to develop prospective trials to examine anthropometric, biochemical, and patient recorded outcomes around nutrition.

Self-reported late effect symptom clusters among young pediatric cancer survivors.

PURPOSE: Most survivors of childhood cancer experience subsequent chronic conditions but little is known about concurrent symptoms. This study seeks to identify late effect symptom clusters among young pediatric cancer survivors. METHODS: Survivors ≥ 18 or parents of survivors < 18 years enrolled in an institutional cohort study indicated (yes/no) if they experienced certain symptoms after treatment. The sample was randomly divided in half for exploratory factor analyses to identify symptom clusters followed by confirmatory factor analyses. Symptoms with ≥ 10% prevalence were included. Cluster structure generalizability across subgroups was examined using congruence coefficients. RESULTS: The sample included 579 survivors (74% non-Hispanic white, 45% leukemia, 12.8 ± 4.5 years at survey, 5.9 ± 3.5 years since therapy). Respondents averaged three symptoms. Three clusters were identified: (1) gastrointestinal: abdominal pain, diarrhea, constipation, nausea, vomiting (Cronbach's α = 0.74); (2) psychological: depression, anxiety, memory problems, anger management problems, sleep problems (α = 0.71); and (3) neurologic: problems walking, numbness/tingling, fatigue, back pain, chronic pain, weakness/inability to move legs (α = 0.71). Confirmatory factor analysis confirmed the three-cluster structure (standardized root mean square residual: 0.09; parsimonious goodness of fit: 0.96; Bentler-Bonett normed fit index: 0.95). The gastrointestinal and psychological clusters were generalizable across most subgroups while the neurologic cluster varied across age and race/ethnicity subgroups. CONCLUSION: Three distinct late effect symptom clusters were identified in young childhood cancer survivors with gastrointestinal and psychological clusters remaining relatively stable across subgroups. Future studies should focus on the characteristics of patients who experience these symptoms, especially those with high symptom burden, and the synergistic impact on quality of life.

Late complications of biliopancreatic diversion in an older patient: a case report.

BACKGROUND: In the mid-seventies, biliopancreatic diversion became popular as weight-loss surgery procedure. This bariatric procedure combines distal gastric resection and intestinal malabsorption, leading to greater weight loss and improvement of co-morbidities than other bariatric procedures. Nowadays, biliopancreatic diversion has become obsolete due to the high risk of nutritional complications. However, current patients with biliopancreatic diversions are aging. Consequently, geriatricians and general practitioners will encounter them more often and will be faced with the consequences of late complications. CASE PRESENTATION: A 74-year old female presented with weakness, recurrent falls, confusion, episodes of irresponsiveness, anorexia and weight loss. Her medical history included osteoporosis, herpes encephalitis 8 years prior and a biliopancreatic diversion (Scopinaro surgery) at age 52. Cerebral imaging showed herpes sequelae without major atrophy. Delirium was diagnosed with underlying nutritional deficiencies. Biochemical screening indicated vitamin A deficiency, vitamin E deficiency, zinc deficiency and severe hypoalbuminemia. While thiamin level and fasting blood glucose were normal. However, postprandial hyperinsulinemic hypoglycemia was observed with concomitant signs of confusion and blurred consciousness. After initiating parenteral nutrition with additional micronutrient supplementation, a marked improvement was observed in cognitive and physical functioning. CONCLUSIONS: Long-term effects of biliopancreatic diversion remain relatively underreported in older patients. However, the anatomical and physiological changes of the gastrointestinal tract can contribute to the development of metabolic and nutritional complications that may culminate in cognitive impairment, functional decline and delirium. Therefore, it is warranted to evaluate the presence of metabolic disturbances and nutritional complications in older patients after biliopancreatic diversion.

Belgian data of ODYSSEY APPRISE: stringent LDL-c targets are in reach when using all available tools.

BACKGROUND: As lipid targets became more stringent in the latest ESC/EAS guidelines, many patients on statin monotherapy are left above their risk-based target, increasing the need for lipid-lowering therapies. The results of the ODYSSEY APPRISE study were recently published by Gaudet et al In this trial, alirocumab (a PCSK9 inhibitor) was investigated in high cardiovascular risk patients in a real-life setting. OBJECTIVE: We aim at analysing the characteristics, safety and efficacy of alirocumab in the Belgian population of the ODYSSEY APPRISE trial and, based on literature research, we aim to evaluate the importance and the need for the add-on, non-statin lipid-lowering therapy in clinical practice. METHODS AND RESULTS: ODYSSEY APPRISE is a multicentric, prospective, single-arm, Phase 3b open-label trial. A total of 68 Belgian patients were enrolled, 63 patients had heterozygous familial hypercholesterolaemia (HeFH). Baseline mean LDL-c was 188.7 mg/dL (SD ± 51.8). At week 12, 65 patients had an evaluable efficacy end point with a mean LDL-c reduction of 59.9% from baseline. The overall incidence of treatment-emergent adverse events (TEAEs) was 75.0%. The most frequent TEAE was back pain (10.3%), nasopharyngitis (10.3%) and injection site erythema (8.8%). Based on the literature, a majority of patients do not reach their risk-based lipid target despite statin therapy alone. CONCLUSION: In a real-life setting, alirocumab is both well-tolerated, safe and very effective in reducing LDL-c in this Belgian cohort. In clinical practice, more patients should be initiated on the add-on, non-statin lipid-lowering therapy in order to reach their risk-based lipid target.

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study.

BACKGROUND: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS: In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER: NCT02413567.