Retrospective study of the clinicopathological characteristics and prognosis of elderly patients with oropharyngeal squamous cell carcinoma

ObjectiveOropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients.MethodsPatients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30–64 years) patient groups to compare the differences.ResultsOf the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS.ConclusionElderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.     

Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma

BACKGROUNDPatients with p16⁺ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16⁺ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16⁺ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning–based metric, the multinucleation index (MuNI), for prognostication in p16⁺ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16⁺ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis–free survival (DMFS) in p16⁺ OPSCC, with HRs of 1.78 (95% CI: 1.37–2.30), 1.94 (1.44–2.60), and 1.88 (1.43–2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain–based digital biomarker test for counseling, treatment, and surveillance of patients with p16⁺ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.     

倾向性评分匹配分析口咽癌PD-L1的表达与HPV感染及预后的相关性研究

目的探讨口咽鳞癌中程序性细胞死亡配体1(PD-L1)与HPV感染状态及患者预后的相关性。方法采用倾向性评分匹配,纳入HPV阳性及HPV阴性口咽癌各50例,对患者进行长期随访,通过免疫荧光检测PD-L1的表达,分析其与HPV感染状态及临床预后的相关性。结果 HPV阳性组及HPV阴性组5年总生存率分别为66%和40%(P=0.003),5年疾病特异性生存率分别为73%和44%(P=0.001)。PD-L1表达率在HPV阳性组较HPV阴性组明显升高(70%vs 42%,P=0.005)。PD-L1与除年龄(P=0.020)外的其他临床病理特征无明显相关性,PDL1阳性为口咽癌独立良好预后因素(DSS,P<0.001;OS,P<0.001)。进一步预后分析提示HPV+/PD-L1+患者较HPV+/PD-L1-者(DSS,P<0.001;OS,P=0.004),HPV-/PD-L1+者(DSS,P=0.010;OS,P=0.047)以及HPV-/PD-L1-者(DSS,P<0.001;OS,P<0.001)具有显著的预后优势。结论 HPV阳性口咽癌患者预后较好,PD-L1在HPV阳性口咽癌中的表达升高,PD-L1阳性可能与HPV阳性口咽癌患者较好的临床预后相关。     

Artificial intelligence for automating the measurement of histologic image biomarkers

Artificial intelligence has been applied to histopathology for decades, but the recent increase in interest is attributable to well-publicized successes in the application of deep-learning techniques, such as convolutional neural networks, for image analysis. Recently, generative adversarial networks (GANs) have provided a method for performing image-to-image translation tasks on histopathology images, including image segmentation. In this issue of the JCI, Koyuncu et al. applied GANs to whole-slide images of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) to automate the calculation of a multinucleation index (MuNI) for prognostication in p16-positive OPSCC. Multivariable analysis showed that the MuNI was prognostic for disease-free survival, overall survival, and metastasis-free survival. These results are promising, as they present a prognostic method for p16-positive OPSCC and highlight methods for using deep learning to measure image biomarkers from histopathologic samples in an inherently explainable manner.     

P16 and HPV discordance in metastatic carcinoma of cervical lymph nodes of unknown primary

The prognostic utility of HPV in oropharyngeal squamous cell carcinoma (OPSCC) and non‐OPSCC as has been well documented. Currently, a standardized IHC scoring system does not exist and is needed to define HPV positivity. We have recently seen a patient that provides a caution in using p16 status as a diagnostic aid.     

Baseline Characteristics May Help Indicate the Best Choice of Health Care Provider for Back Pain Patients in Primary Care: Results From a Prospective Cohort Study

ObjectiveBaseline characteristics of patients low back pain differ substantially between care settings, but it is largely unknown whether predictors are of equal importance across settings. The aim of this study was to investigate whether 8 known predictors relate differently to outcomes in chiropractic practice and in general practice and to which degree these factors may be helpful in selecting patients benefiting more from one setting or the other.MethodsPatient characteristics were collected at baseline, and outcomes of pain intensity (numeric rating scale 0-10) and activity limitation (Roland-Morris Disability Questionnaire 0-100) after 2, 12, and 52 weeks. Differences in the prognostic strength between settings were investigated for each prognostic factor separately by estimating the interaction between setting and the prognostic factor using regression models. Between-setting differences in outcome in high-risk and low-risk subgroups, formed by single prognostic factors, were assessed in similar models adjusted for a propensity score to take baseline differences between settings into account.ResultsPrognostic factors were generally associated more strongly with outcomes in general practice compared with chiropractic practice. The difference was statistically significant for general health, duration of pain, and musculoskeletal comorbidity. After propensity score adjustment, differences in outcomes between settings were insignificant, but negative prognostic factors tended to be less influential in chiropractic practice except for leg pain and depression, which tended to have less negative impact in general practice.ConclusionKnown prognostic factors related differently to outcomes in the 2 settings, suggesting that some subgroups of patients might benefit more from one setting than the other.     

Design considerations for a study to evaluate the impact of smoking cessation treatment on stimulant use outcomes in stimulant-dependent individuals

Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality, yet, the provision of smoking cessation treatment in conjunction with substance use disorder (SUD) treatment is not standard practice. This is due, in part, to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes. The NIDA Clinical Trials Network is conducting a 10-week, two-group, randomized trial to evaluate the impact of providing smoking cessation treatment (SCT) with SUD treatment as usual (TAU), compared to TAU alone, in smokers who are in outpatient treatment for cocaine or methamphetamine dependence. Approximately 528 participants, recruited from 12 community treatment programs, will be randomized into the trial. The present paper describes key design decisions made during protocol development. The trial is designed to evaluate the relationship between cigarette smoking and stimulant use, which prior research suggests is linked, and should contribute to our understanding of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence. Unique aspects of the trial include the primary question of interest, which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes, and the intensity of the SCT chosen, which includes bupropion, nicotine replacement, and two psychosocial interventions.     

Hospital outcomes associated with new-onset atrial fibrillation during ICU admission: A multicentre competing risks analysis

PurposeNew onset atrial fibrillation (NOAF) in critically ill patients has been associated with increased short-term mortality. Analyses that do not take into account the time-varying nature of NOAF can underestimate its association with hospital outcomes.We investigated the prognostic association of NOAF with hospital outcomes using competing risks methods.Materials and methodsWe undertook a retrospective cohort study in three general adult intensive care units (ICUs) in the UK from June 2008 to December 2015. We excluded patients with known prior atrial fibrillation or an arrhythmia within four hours of ICU admission.To account for the effect of NOAF on the rate of death per unit time and the rate of discharge alive per unit time we calculated subdistribution hazard ratios (SDHRs).ResultsOf 7541 patients that fulfilled our inclusion criteria, 831 (11.0%) developed NOAF during their ICU admission. NOAF was associated with an increased duration of hospital stay (CSHR 0.68 (95% CI 0.63–0.73)) and an increased rate of in-hospital death per unit time (CSHR 1.57 (95% CI 1.37–1.1.81)). This resulted in a strong prognostic association with dying in hospital (adjusted SDHR 2.04 (1.79–2.32)). NOAF lasting over 30 min was associated with increased hospital mortality.ConclusionsUsing robust methods we demonstrate a stronger prognostic association between NOAF and hospital outcomes than previously reported.     

Pain, disability, and satisfaction outcomes and predictors of outcomes: a practice-based study of chronic low back pain patients attending primary care and chiropractic physicians

BACKGROUND: Few studies exist on the prognostic value of demographic, clinical, or psychosocial factors on long-term outcomes for patients with chronic low back pain. OBJECTIVE: This study reports on long-term pain and disability outcomes for patients with chronic low back pain, evaluates predictors of long-term outcomes, and assesses the influence of doctor type on clinical outcome. METHODS: Sixty chiropractic (DC) and 111 general practice (MD) physicians participated in data collection for a prospective, longitudinal, practice-based, observational study of ambulatory low back pain of mechanical origin. The primary outcomes, measured at 6 months and 12 months, were pain (by using the Visual Analog Scale), and functional disability (by using the Revised Oswestry Disability Questionnaire). Satisfaction was a secondary outcome. RESULTS: Overall, long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians. Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee. However, an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts (adjusted differences = 8.0 to 15.2; P <.002). A greater proportion of chiropractic patients were satisfied with all aspects of their care (P =.0000). The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes. Income, smoking, comorbidity, and chronic depression were also identified as predictors of outcomes in this study. CONCLUSION: Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes. Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction. Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians' practice activities that better serve these patients' needs.     

Smoking relapse-prevention intervention for cancer patients: Study design and baseline data from the surviving SmokeFree randomized controlled trial

Continued smoking after a cancer diagnosis contributes to several negative health outcomes. Although many cancer patients attempt to quit smoking, high smoking relapse rates have been observed. This highlights the need for a targeted, evidence-based smoking-relapse prevention intervention. The design, method, and baseline characteristics of a randomized controlled trial assessing the efficacy of a self-help smoking-relapse prevention intervention are presented. Cancer patients who had recently quit smoking were randomized to one of two conditions. The Usual Care (UC) group received the institution's standard of care. The smoking relapse-prevention intervention (SRP) group received standard of care, plus 8 relapse-prevention booklets mailed over a 3 month period, and a targeted educational DVD developed specifically for cancer patients. Four hundred and fourteen participants were enrolled and completed a baseline survey. Primary outcomes will be self-reported smoking status at 6 and 12-months after baseline. Biochemical verification of smoking status was completed for a subsample. If found to be efficacious, this low-cost intervention could be easily disseminated with significant potential for reducing the risk of negative cancer outcomes associated with continued smoking.     

Autologous venous bypass in the therapy of arterial occlusive disease of the femoropopliteal area: long-term results

The outcome of 532 femoro-popliteal vein grafts performed electively during the years 1970 to 1985 for obliterative arterial disease, was analyzed using the documentation-system of the Austrian Society for Vascular Surgery, as well as SAS and BMDP-software on an IBM 4381 computer of the Medical Faculty. The probability of function was estimated according to the Kaplan-Meier method, statistical differences were checked with Breslow's and Mantel's test, the proportional hazards regression model (Cox) was used to elucidate the influence of different risk factors on each own and in combination of each other. In the univariate analysis, the preoperative clinical status was found to be of prognostic significance, but technical details such as intraoperative as well as postoperative arteriography or site of the distal anastomosis were not important. A postoperative coumarine treatment had no demonstrable impact on graft function, but positively influenced the probability of patient survival. Taking into account the factors found to be of significance in the univariate analysis (e.g. set of factors: site of distal anastomosis, diabetic state and smoking habits) were analyzed using the proportional hazards regression model but were found of no major influence. The factors preoperative clinical status, patients age, and coumarine therapy significantly influenced the probability of patient survival, but diabetes mellitus and smoking were found to be not important.     

Reorganizing the delivery of intensive care could improve efficiency and save lives

Critically ill patients are at high risk for death and permanent disability. Their care is also very expensive. The method of delivering critical care services to these patients can have an impact on their clinical and economic outcomes. Researchers face significant challenges when attempting to identify an association between an intensive care unit (ICU) organizational characteristic and patient outcomes. In this paper we review the challenges faced when evaluating the impact of ICU organizational characteristics on patient outcomes and highlight ICU characteristics that are consistently associated with improved patient outcomes. These characteristics include: (i) the presence of specialist physicians devoted to the ICU; (ii) increased nurse : patient ratios; (iii) decreased use of tests and evaluations that will not change clinical management; (iv) development and implementation of evidence-based protocols and guidelines; (v) use of computer-based alerting and reminding systems; and (vi) having a pharmacist participate in daily rounds in the ICU. When implementing these in ICUs, it is important to evaluate the impact of these characteristics on patient outcomes. We provide a format for such an evaluation. Given the growing evidence supporting the association between specific ICU characteristics and improved patient outcomes, we hope the future realizes broad implementation of these beneficial characteristics.     

Smoking increases risk of tooth loss: A meta-analysis of the literature

AIM: To quantitatively evaluate the impact of smoking on tooth loss. METHODS: We performed a PubMed search to identify published articles that investigated the risk of tooth loss by smoking, from which RRs and their variance with characteristics of each study were extracted. The random-effects models were used to derive a pooled effect across studies. Potential sources of heterogeneity on the characteristics of the study and their influence on the pooled effect size were investigated using meta-regression models. RESULTS: We identified 24 studies containing a total of 95973 participants for analysis. The pooled RR of ever-smokers compared with never- smokers was 1.73 (95%CI: 1.60-1.86, P < 0.001). In meta-regression analysis, only the mean age of participants alone was identified as a statistically significant source of heterogeneity. The effect of smoking on tooth loss was stronger when the mean age of study participants was higher, indicating possible enhancement of tooth loss due to aging by smoking. RR was significantly lower in former smokers (1.49, 95%CI: 1.32-1.69, P < 0.001) than in current smokers (2.10, 95%CI: 1.87-2.35, P < 0.001), indicating the substantial benefit of smoking cessation for reducing the risk of tooth loss. CONCLUSION: Smoking is an independent risk factor for tooth loss regardless of many other confounders. Smoking cessation may attenuate this effect.     

The effect of a multi-component smoking cessation intervention in African American women residing in public housing

The purpose of this study was to test the effectiveness of a multi-component smoking cessation intervention in African American women residing in public housing. The intervention consisted of: (a) nurse led behavioral/empowerment counseling; (b) nicotine replacement therapy; and, (c) community health workers to enhance smoking self-efficacy, social support, and spiritual well-being. The results showed a 6-month continuous smoking abstinence of 27.5% and 5.7% in the intervention and comparison groups. Changes in social support and smoking self-efficacy over time predicted smoking abstinence, and self-efficacy mediated 6-month smoking abstinence outcomes. Spiritual well-being did not predict or mediate smoking abstinence outcomes. These findings support the use of a nurse/community health worker model to deliver culturally tailored behavioral interventions with marginalized communities.     

Improving outcomes for patients hospitalized with CHF

Congestive Heart Failure is a costly debilitating medical condition that affects millions of elderly people. This Clinical Practice Improvement study was under taken to determine how variation in patient characteristics and clinical processes impact patient outcomes including length of stay, total charges, and increased severity of illness during hospitalization. The AHCPR Guideline for Heart Failure was used to evaluate clinical care. Data on patient characteristics including severity of illness and process of care were analyzed to determine which variables had the greatest impact on outcomes of care. Results showed that patient characteristics including comorbidities, severity of illness, and noncompliance with diet were significantly related to longer lengths of stay, higher charges, and/or increased severity (all covariates, p < .05). In addition, process of care variables including medication use and patient education significantly (p < .05) impacted outcomes of care. Findings have implications for the development of practice guidelines designed to improve patient outcomes associated with CHF hospitalizations.     

YMCA exercise intervention to augment smoking cessation treatment in adults with high anxiety sensitivity: Study protocol for a randomized controlled trial

Extant evidence suggests that exercise can reduce anxiety related vulnerability factors, such as anxiety sensitivity (AS), or fear of bodily sensations related to anxiety, that negatively impact smoking cessation outcomes. Building upon emerging evidence supporting the efficacy of exercise as an aid for smoking cessation in adults with high AS, we are conducting a trial to examine the efficacy and feasibility of this clinical application when implemented in a community setting. Partnering with the YMCA, this study aims to enroll 150 adults in a standard smoking cessation protocol (i.e. counseling and nicotine replacement therapy) and randomly assign them to either 15 weeks of programmed vigorous-intensity or low-intensity exercise. Smoking abstinence data will be collected up to 6 months following the quit attempt.     

Smoking cessation interventions in chronic obstructive pulmonary disease and the role of the family: a systematic literature review

AIM: This paper is a report of a systematic review to assess the effectiveness of family-focused smoking cessation interventions for people with chronic obstructive pulmonary disease and to determine what data on families are documented in studies of smoking cessation interventions. BACKGROUND: Chronic obstructive pulmonary disease is a major public health problem and cigarette smoking is the most important factor contributing to its development and progression. However, smoking cessation rates are low and relapse is common. The role of families in smoking cessation efforts has received little attention. METHODS: All studies were included in the review that (i) addressed an evaluation of a psycho-social/educational smoking cessation intervention for people with chronic obstructive pulmonary disease, (ii) addressed some information on the family (i.e. living arrangements, marital status, smoking history of family members, support for quitting) and/or included the family as part of the intervention and (iii) were published between 1990 and 2006. Electronic data sources, existing systematic reviews of smoking cessation interventions and the grey literature were reviewed. RESULTS: Seven studies were included. Six studies (11 papers) included data on marital status, smoking status of household members, support for quitting smoking and related variables. In two of the studies, the variable on the family was used to analyse smoking cessation outcomes. One additional study met the inclusion criterion of an evaluation of a smoking cessation intervention, which also included a family focus in the intervention. CONCLUSION: No conclusions about the effectiveness of a family-focused smoking cessation intervention could be drawn from this review. Further research is needed to determine if a more family-focused intervention, in conjunction with pharmacological and counselling approaches, would lead to improved smoking cessation outcomes.     

Evidence-based practice to assist women in hospital settings to quit smoking and reduce cardiovascular disease risk

Smoking and obesity are widely recognized cardiovascular risk factors for significant morbidity and mortality in women. Although women still smoke less than men do, smoking among women is on the increase, especially in younger women and teenagers. Reduction of cardiovascular risk through smoking cessation while maintaining weight is a major goal of intervention. The purpose of this article is to discuss best care practices for women with tobacco addiction using a 3-point integration of clinical expertise, the best available evidence gained from systematic research, and an analysis of satisfaction with care data. A model for a smoking cessation intervention with weight management content is presented using a conceptual framework of social learning theory, self-efficacy judgments, and the 4 principal sources of self-efficacy information. The specific aims of this pilot study are to (1) test the feasibility of the study methods and procedures, including subject accrual, attrition, and reliability of the instruments and protocol; (2) explore utilization of and satisfaction with the intervention; and (3) describe the impact of the intervention on primary (smoking biomarker) and secondary (weight/body mass index, depression, partner support, and smoking cessation self-efficacy temptations) outcomes. Results show that the study is feasible, but modifications are needed to improve utilization and satisfaction with care. The primary outcome showed a reduction in the smoking biomarker while maintaining weight at the 2-month follow-up. There was also improvement in skills to manage temptation situations that supported the conceptual framework. Hypotheses are presented for a future experimental study.