The health care delivery system in the United States is challenged to meet the needs of a growing population of cancer survivors. A pressing need is to optimize overall function and reduce disability ...in these individuals. Functional impairments and disability affect most patients during and after disease treatment. Rehabilitation health care providers can diagnose and treat patients' physical, psychological, and cognitive impairments in an effort to maintain or restore function, reduce symptom burden, maximize independence and improve quality of life in this medically complex population. However, few care delivery models integrate comprehensive cancer rehabilitation services into the oncology care continuum. The Rehabilitation Medicine Department of the Clinical Center at the National Institutes of Health with support from the National Cancer Institute and the National Center for Medical Rehabilitation Research convened a subject matter expert group to review current literature and practice patterns, identify opportunities and gaps regarding cancer rehabilitation and its support of oncology care, and make recommendations for future efforts that promote quality cancer rehabilitation care. The recommendations suggest stronger efforts toward integrating cancer rehabilitation care models into oncology care from the point of diagnosis, incorporating evidence-based rehabilitation clinical assessment tools, and including rehabilitation professionals in shared decision-making in order to provide comprehensive cancer care and maximize the functional capabilities of cancer survivors. These recommendations aim to enable future collaborations among a variety of stakeholders to improve the delivery of high-quality cancer care.
Summary Background Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive ...lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects. Methods This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. Findings Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR–0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (−0·03 T/S units, −0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02–0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (–2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (–3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72–1·20, p=0·57). Interpretation Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding. Funding US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.
Abstract Objective Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque ...destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques. This study characterized inflammation in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) as a magnetic resonance imaging (MRI) probe. Methods DT-MPIO were used to detect and characterize inflammatory markers, vascular cell adhesion molecule 1 (VCAM-1). and P-selectin on (1) tumor necrosis factor-α-treated cells by immunocytochemistry and (2) aortic root plaques of apolipoprotein-E deficient mice by in vivo MRI. Furthermore, apolipoprotein E-deficient mice with focal carotid plaques of different phenotypes were developed by means of periarterial cuff placement to allow in vivo molecular MRI using these probes. The association between biomarkers and the magnetic resonance signal in different contrast groups was assessed longitudinally in these models. Results Immunocytochemistry confirmed specificity and efficacy of DT-MPIO to VCAM-1 and P-selectin. Using this in vivo molecular MRI strategy, we demonstrated (1) the DT-MPIO-induced magnetic resonance signal tracked with VCAM-1 ( r = 0.69; P = .014), P-selectin ( r = 0.65; P = .022), and macrophage content ( r = 0.59; P = .045) within aortic root plaques and (2) high-risk inflamed plaques were distinguished from noninflamed plaques in the murine carotid artery within a practical clinical imaging time frame. Conclusions These molecular MRI probes constitute a novel imaging tool for in vivo characterization of plaque vulnerability and inflammatory activity in atherosclerosis. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid atherosclerotic disease in the future.
Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic ...counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.
In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium ICGC PedBrain, Medulloblastoma Advanced Genomics International Consortium MAGIC, and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.
We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence 14% in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five 71% of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight 57% of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.
Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.
German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore ...acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge.
Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT.
Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy.
Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient, impairment in sexual function may persist after the completion of therapy and merits further investigation.
Transitional Age Youth and College Mental Health Chan, Vivien; Moore, Jessica; Derenne, Jennifer ...
Child and adolescent psychiatric clinics of North America,
07/2019, Letnik:
28, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Transitional age youth with a history of mood disorders, such as major depressive disorder, are uniquely vulnerable to clinical destabilization and relapse in the context of life transition. Moving ...from a structured adolescence to a more independent and potentially more demanding young adult life can result in worsening symptoms and barriers to effective help-seeking. Transitional age youth newly diagnosed are exposed to their first course of treatment of a potentially chronic condition. This article describes the challenges inherent in navigating this life transition, and also offers strategies to promote a successful “launch” into adulthood.
SUMMARY Evidence suggests that early exposure to surgical techniques, surgical knowledge and mentors strongly correlates with students’ interest, knowledge and confidence in general surgery as a ...postgraduate career choice. Preclerkship exposure to surgery and implementation of a formal surgical curriculum is often restricted owing to attending surgeon time commitments and cost limitations. To promote earlier exposure to surgery, a group of senior medical students at McMaster University, Hamilton, Ont., developed and implemented a novel pilot program with a surgical lecture series and a surgical skills laboratory for preclerkship students. This commentary discusses the effectiveness of these initiatives.
Objective: The COVID-19 pandemic has increased psychological distress among common people and has caused health care providers, such as nurses, to experience tremendous stress. Methods: This ...prospective cross-sectional study assessed the psychological impacts on nurses in a community hospital in Taiwan, including major depressive disorder (MDD), posttraumatic stress (PTS), and pessimism. According to transactional theory, coping strategies and personal factors have psychological impacts. We hypothesized that behavioral responses to COVID-19 (problem-focused coping) are more effective in reducing psychological impacts than emotional responses to COVID-19 (emotion-focused coping). Independent variables were the use of behavioral and emotional coping strategies for COVID-19 and 3 personal factors, namely sleep disturbance, physical component summary (PCS-12), and mental component summary (MCS-12) of the 12-Item Short Form Health Survey (SF-12) obtained from the Medical Outcomes Study. Dependent variables comprised 3 psychological impacts, namely MDD, PTS, and pessimism. Results: We determined that behavioral coping strategies had significant negative effects on PTS and pessimism; however, emotional coping strategies had significantly positive effects on PTS and pessimism. Sleep disturbance was significantly associated with increased MDD and pessimism. PCS-12 had a significant negative effect on PTS, whereas MCS-12 was not significantly associated with any of the 3 psychological impacts. Conclusions: Nurses who adopted protective behavior against COVID-19, such as washing hands, wearing masks, avoiding touching eyes, and mouth, and avoiding personal contact, were associated with less posttraumatic stress and pessimism. Healthcare providers should consider strategies for improving preventive behaviors to help ease their worries and fears concerning COVID-19.
Objective To evaluate the effectiveness of a second newborn screen for congenital adrenal hyperplasia (CAH) in the state of Colorado and report characteristics associated with cases identified on the ...first versus second screen. Study design Colorado implemented newborn screening for CAH with 17-hydroxyprogesterone beginning August 2000. The first screening is performed within 72 hours of life and the second between 8 and 14 days of life. We compared infants diagnosed on the basis of the first versus second newborn screen. Results The first screen identified 29 cases of which 28 represented classical CAH. The incidence of classical CAH on the first screen was 1:24 766. The second screen identified 17 additional cases, of which 11 represented classical CAH. Combined, the incidence of classical CAH was 1:17 789. The sensitivity of the first screen was 71.79%. The false negative rate of the first screen was 28.2%. In the absence of a second screen, 1:47 824 infants would have been missed. Infants diagnosed on the first screen had higher 17-hydroxyprogesterone values compared with those diagnosed on the second screen ( P = .0008). Conclusions The use of a single newborn screen for CAH missed nearly 30% of classical CAH cases in Colorado. Addition of a second screen, therefore, can improve the operating characteristics of the newborn screening program.
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