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Background and Aims Combination atezolizumab/bevacizumab is the gold standard for first-line treatment of unresectable hepatocellular carcinoma (HCC). Our study investigated the efficacy and safety of combination therapy in older patients with HCC. Methods 191 consecutive patients from eight centres receiving atezolizumab and bevacizumab were included. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in older (age ≥ 65 years) and younger (age

Background Non‐bullous pemphigoid (NBP) is a pemphigoid variant which frequently resembles other pruritic skin diseases. In contrast with bullous pemphigoid (BP), blisters are absent. In BP, previous studies showed that IgE autoantibodies may be involved in its pathogenesis. IgE‐activated mast cells, basophils and eosinophils may participate in BP by inducing pruritus and possibly blister formation, although the differential role of IgE in NBP compared with BP has not yet been described. Objective To assess IgE in serum and skin of NBP and BP patients. Methods We examined total IgE and pemphigoid‐specific IgE in the serum of 68 NBP and 50 BP patients by enzyme‐linked immunosorbent assay (ELISA). Sera of 25 pemphigus patients and 25 elderly patients with pruritus were included as controls. Skin biopsies of 14 NBP and 14 BP patients with the highest IgE titres to NC16A were stained for IgE by immunofluorescence techniques. Results Total IgE was elevated in 63% of NBP and 60% of BP patients, and in 20% of pemphigus controls, as well as 60% of elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, P = 0.139; BP230 34% vs. 22%, P = 0.149). IgE ELISAs for NC16A and BP230 were positive in 8% and 20% of elderly controls, respectively, while all pemphigus controls were negative. Two of 28 biopsies (7%; one NBP, one BP) showed linear IgE along the basement membrane zone, while in most biopsies (71% NBP; 86% BP) IgE was bound to dermal cells. Conclusion Since IgE was present in the serum and skin of both NBP and BP patients, this supports IgE‐dependent mechanisms common to both diseases, such as pruritus. However, it remains to be elucidated whether IgE contributes to blister formation in BP., Linked Commentary: I. Kortekaas Krohn. J Eur Acad Dermatol Venereol 2021; 35: 781–782. https://doi.org/10.1111/jdv.17164.

Aims:\ud Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up‐titration of angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta‐blockers on outcome across the age spectrum in HFrEF patients.\ud \ud Methods and results:\ud We analysed HFrEF patients on sub‐optimal doses of ACEI/ARB and/or beta‐blockers from the BIOSTAT‐CHF study stratified by age. Patients underwent a 3‐month up‐titration period. We used inverse probability weighting to adjust for the likelihood of successful up‐titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow‐up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta‐blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI‐ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P

OBJECTIVES: To evaluate long-term survival and institutionalization in onco-geriatric surgical patients, and to analyze the association between these outcomes and a preoperative risk score. DESIGN: Prospective cohort study with long-term follow-up. SETTING: International and multicenter locations. PARTICIPANTS: Patients aged 70 years or older undergoing elective surgery for a malignant solid tumor at five centers (n = 229). MEASUREMENTS: We assessed long-term survival and institutionalization using the Preoperative Risk Estimation for Onco-geriatric Patients (PREOP) score, developed to predict the 30-day risk of major complications. The PREOP score collected data about sex, type of surgery, and the American Society for Anesthesiologists classification, as well as the Timed Up & Go test and the Nutritional Risk Screening results. An overall score higher than 8 was considered abnormal. RESULTS: We included 149 women and 80 men (median age = 76 y; interquartile range = 8). Survival at 1, 2, and 5 years postoperatively was 84%, 77%, and 56%, respectively. Moreover, survival at 1 year was worse for patients with a PREOP risk score higher than 8 (70%) compared with 8 or lower (91%). Of those alive at 1 year, 43 (26%) were institutionalized, and by 2 years, almost half of the entire cohort (46%) were institutionalized or had died. A PREOP risk score higher than 8 was associated with increased mortality (hazard ratio = 2.6; 95% confidence interval [CI] = 1.7-4.0), irrespective of stage and age, but not with being institutionalized (odds ratios = 1 y, 1.6 [95% CI =.7-3.8]; 2 y, 2.2 [95% CI =.9-5.5]). CONCLUSION: A high PREOP score is associated with mortality but not with remaining independent. Despite acceptable survival rates, physical function may deteriorate after surgery. It is imperative to discuss treatment goals and expectations preoperatively to determine if they are feasible. Using the PREOP risk score can provide an objective measure on which to base decisions. J Am Geriatr Soc 68:1235–1241, 2020.

European journal of heart failure (2020). doi:10.1002/ejhf.1749, Published by Wiley, Oxford

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with Y-90-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade >= 3 adverse events from start of Y-90-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to Y-90-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after Y-90-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of Y-90-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and Y-90-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with Y-90-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it.

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with Y-90-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade >= 3 adverse events from start of Y-90-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to Y-90-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after Y-90-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of Y-90-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and Y-90-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with Y-90-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effects of pharmacological agents for neurogenic oropharyngeal dysphagia based on evidence from randomized controlled trials (RCTs). METHODS: Electronic databases were systematically searched between January 1970 and March 2021. Two reviewers independently extracted and synthesized the data. The outcome measure was changed in (any) relevant clinical swallowing-related characteristics. KEY RESULTS: Data from 2186 dysphagic patients were collected from 14 RCT studies across a range of pharmacotherapies. The pooled effect size of transient receptor potential (TRP) channel agonists was large compared to placebo interventions (SMD[95%CI] =1.27[0.74,1.80], p

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed in advanced stage and therefore requires aggressive, multimodal treatment. Elderly patients are often excluded from standard therapy regimens purely based on age. This clinical review aims to collect all published data in the literature on treatment modality selection in elderly patients and on age-related adverse events following treatment of HNSCC. We performed a literature search for articles on the treatment of HNSCC in elderly patients. Most of the articles were retrospective studies with the consequent limitations. It can be concluded that age is not an absolute contraindication for intensive treatment and comorbidity is an important predictor of outcome, but not the only one. Despite the existence of multiple tools for pretreatment evaluation, there are not consistent data on their use.

Background Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. Aims To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose-, blood pressure- or lipid-lowering medications in people with diabetes. Methods A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. Results Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA(1c)levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose-lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA(1c). Conclusions Deprescribing of glucose-lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure- and lipid-lowering medications in people with diabetes are needed.

ObjectivesTo summarize the evidence on the prevalence and preventability of drug-related hospital readmissions.DesignA systematic review was performed of studies that examined drug-related hospital readmissions. PubMed, EMBASE, and the Cochrane Library were searched from inception through August 2016. Reference lists and a citation analysis on Web of Science and Scopus were also consulted. Two reviewers extracted study data with dual assessment of risk of bias. Prevalence and preventability of readmission due to drugs were calculated. Data were qualitatively summarized according to outcome.ResultsNineteen studies met the eligibility criteria. Nine measured readmissions due to drug-related problems, seven due to adverse drug reactions, two due to adverse drug events, and one due to drug-drug interactions. Rates of readmissions due to drugs varied from 3% to 64% (median 21%, interquartile range (IQR) 14-23%). Readmissions were deemed preventable in 5% to 87% of cases (median 69%, IQR 19-84%). Evidence regarding the risk factors for drug-related readmissions and drugs causing these readmissions was inconsistent.ConclusionAlthough studies show high variability in prevalence and preventability of drug-related hospital readmissions, readmissions due to drugs seem to occur often, especially in older adults. Further research is needed to specify the causes of preventable readmissions and implement effective interventions to reduce medication-related hospital admissions.

The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone.Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present.Registered in the Dutch trial register www. trialregister.nl, NTR1757; EudraCT number 2006-002141-37.

OBJECTIVE: Thoughts of death are not regularly included in diagnostic instruments and rarely examined separately from thoughts of suicide. This exploratory study examined whether thoughts of death and thoughts of suicide affect the course of late-life depressive disorders.METHODS: In 378 depressed older persons, thoughts of death and thoughts of suicide were assessed using questions from the Composite International Diagnostic Interview. After 2 years, the presence of a DSM-IV-TR diagnosis of minor or major depression or dysthymia was assessed with the Composite International Diagnostic Interview. The Inventory of Depressive Symptomatology was administered every 6 months up till 3-year follow-up.RESULTS: Multinomial logistic regression showed that thoughts of death as well as thoughts of suicide predicted double depression at follow-up (OR = 2.14 [95% CI: 1.04-4.40] and OR = 6.47 [95% CI: 2.22-3.02], respectively), compared with patients without these thoughts. Results became non-significant when adjusted for baseline depression severity (OR = 1.17 [95% CI: 0.52-2.63] and OR = 2.57 [95% CI: 0.79-8.84], respectively). Mixed linear models showed that severity of depression was lowest in the reference group, while symptoms decreased more over time in those with either thoughts of death or suicide.CONCLUSIONS: Patients with thoughts of death or with thoughts of suicide were more severely depressed at baseline and follow-up, with the highest risk of being depressed at follow-up for patients with thoughts of suicide. These associations could be explained by baseline depression severity. The results suggest that thoughts of death and thoughts of suicide are important risk markers in predicting the course of depression.

Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with age and are associated with depression, these characteristics are likely to modify the treatment outcome of antidepressant drugs in late-life depression. This review examines how these five characteristics are taken into account in randomised controlled trials (RCTs) with antidepressant drugs for major depressive disorder in patients aged 60 years or above.Design: A systematic search in PubMED, PsychInfo and EMBASE, from the year 2000 onwards, yielded 27 RCTs, with a total of 6356 subjects with a median age of 71 years. Two reviewers independently assessed whether each characteristic was considered as inclusion or exclusion criterion, descriptive variable, stratification variable, co-variable, outcome measure, or in adverse effect monitoring.Results: Malnutrition and frailty were not taken into account in any study. Disability was used as an outcome measure in five studies. Two studies explicitly included a population with possibly serious medical co-morbidity. Cognitive status was the only condition taken into account as co-variable (n = 3) or stratifying variable (n = 1) and was used as outcome measure in seven studies.Conclusions: We conclude that geriatric characteristics are rarely taken into account in RCTs on anti-depressant drugs in late-life depression, and studies including the oldest adults are underrepresented. This warrants recruitment of the oldest adults and adjustment of treatment strategies in future studies. Copyright (C) 2016 John Wiley & Sons, Ltd.

AIM: Colon cancer resection in a non-elective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on non-elective resection.METHOD: Data were obtained from the Dutch Surgical Colorectal Audit. Patients undergoing colon cancer resection in the Netherlands between January 2009 and December 2013 were included. Patient, treatment and tumour factors were analyzed in relation to the urgency of surgery. The primary outcome was the thirty day postoperative mortality.RESULTS: The study included 30,907 patients. In 5934 (19.2%) of patients, a non-elective colon cancer resection was performed. There was a 4.4% overall mortality rate, with significantly more deaths after non-elective surgery (8.5% vs 3.4%, PCONCLUSION: Non-elective colon cancer resection is associated with high mortality. In particular, right-sided resections and patients with tumour perforation are at particularly high risk. The optimization of patients prior to surgery and expeditious operation after diagnosis might prevent the need for a non-elective resection. This article is protected by copyright. All rights reserved.

According to the established validation protocols, a typical validation study of a blood pressure (BP) monitor includes general population adults with normal or elevated BP. It is recognized, however, that the automated (oscillometric) BP monitors may have different accuracy or uses in some special populations compared with adults in the general population. Thus, an automated BP monitor with proven accuracy in a general population of adults may not be accurate in a special population, and therefore separate validation is needed. Recognized special populations deserving separate validation are those for which there is theoretical, and also clinical evidence, that the accuracy of BP monitors in these groups differs from that in the general population. Young children, pregnant women (including those with preeclampsia), individuals with arm circumference >42 cm, and patients with atrial fibrillation are regarded as special populations. Adolescents, individuals older than 80 years, and patients with end-stage renal disease or diabetes mellitus have also been considered as possible special groups, but there is still inadequate evidence of altered accuracy of BP monitors in these subjects. Validation studies should be performed in special populations and evaluated separately after the BP-measuring device has successfully undergone a validation study in a general population (unless the test device is intended only for a special population). This article discusses issues relating to the measurement of BP and the diagnosis of hypertension in selected special populations, as well as in low-resource settings, where a simplified yet efficient evaluation strategy is necessary. ispartof: pages:1122-1127 ispartof: JOURNAL OF CLINICAL HYPERTENSION vol:20 issue:7 pages:1122-1127 ispartof: location:United States status: published

Rates of population ageing are unprecedented and this, combined with the progressive urbanization of lifestyles, has led to a dramatic shift in the epidemiology of diabetes towards old age, particularly to those aged 60-79 years. Both ageing and diabetes are recognized as important risk factors for the development of functional decline and disability. In addition, diabetes is associated with a high economic, social and health burden. Traditional macrovascular and microvascular complications of diabetes appear to account for less than half of the diabetes-related disability observed in older people. Despite this, older adults are under-represented in clinical trials. Guidelines from organizations such as the National Institute for Health and Care Excellence (NICE), the European Association for the Study of Diabetes, and the American Diabetes Association acknowledge the need for individualized care, but the glycaemic targets that are suggested to constitute good control [HbA1c 53-59 mmol/mol (7-7.5%)] are too tight for frail older individuals. We present a framework for the assessment of older adults and guidelines for the management of this population according to their frailty status, with the intention of reducing complications and improving quality of life for these people. This article is protected by copyright. All rights reserved.

BACKGROUND: Addition of assessment of comorbid diseases ('D') and oxygen saturation ('S') to the CRB-65 score has been recommended to improve its accuracy for risk stratification in community-acquired pneumonia (CAP). The aim of the present study was to validate the resulting DS-CRB-65 score in a large cohort of patients with CAP. METHODS: A total of 4432 patients prospectively enrolled in the CAPNETZ cohort were included in the present study. Predefined endpoints were 28-day mortality, requirement for mechanical ventilation or vasopressors (MV/VS) and requirement for MV/VS or intensive care unit admission (MV/VS/ICU). Receiver operating characteristic curve analysis was used to determine the accuracy of the CRB-65 score and the addition of D (extra-pulmonary comorbidities) and S (oxygen saturation

BACKGROUND: The purpose of this study was to reveal prognostic factors for surgical complications and survival in young and elderly patients with malignant salivary gland tumors.METHODS: Retrospective analysis of surgically treated patients with malignant major salivary gland tumors was performed. Of the 111 patients, 33 patients were 70 years or older and 78 patients were under 70. Comorbidity was recorded using the Adult Comorbidity Evaluation-27 index and complications using the Clavien-Dindo classification.RESULTS: Comorbidity and complications were significantly more frequent in elderly patients (p < .05). Age, comorbidity, and length of surgery were not significant independent predictors of complications. Stage was the only independent predictive factor for postoperative complications and disease-specific survival.CONCLUSION: Based on this retrospective analysis reviewing surgically treated patients, age alone should not be a reason to treat elderly patients differently, as it was not a predictor of either complications or disease-specific survival.

AimsThe Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formulae are often used to estimate glomerular filtration rate (GFR). The objective was to determine the best method for estimating GFR in older adults.MethodsA cross-sectional study was conducted at the geriatric wards of two hospitals in The Netherlands. Patients aged 70 years or above with an estimated (e)GFR below 60mlmin(-1)1.73m(-2) were included. The CG, CG calculated with ideal bodyweight (IBW), MDRD and CKD-EPI formulae were compared with a criterion standard, sinistrin clearance. Renal function was classified into five stages according to the National Kidney Foundation Disease Outcomes Quality Initiative chronic kidney disease classification, as follows (in mlmin(-1)1.73m(-2)): stage1, eGFR90; stage2, eGFR of 60-89; stage3, eGFR of 30-59; stage4, eGFR of 15-29; and stage 5, eGFRResultsSixteen patients, 50% male, with a mean age of 82 years (range 71-87years) and mean body mass index 26kgm(-2) (range 18-36kgm(-2)), were included. On average, all formulae slightly overestimated GFR, as follows (in mlmin(-1)1.73m(-2)): CG +0.05 [95% confidence interval (CI) -28 to +28]; CG with IBW +0.03 (95% CI -20 to +20); MDRD +9 (95% CI -16 to +34); and CKD-EPI +5 (95% CI -20 to +29). They classified kidney disease correctly in 68.8% (CG), 75% (CG with IBW), 43.8% (MDRD) and 68.8% (CKD-EPI) of the participants, respectively.ConclusionsThe CG, CG with IBW, MDRD and CKD-EPI formulae estimate the mean GFR of a population rather well. In individual cases, all formulae may misclassify kidney disease by one stage.

Objective This study aimed to establish whether antipsychotic (AP) use in patients with dementia negatively affects quality of life (QoL) independent of neuropsychiatric symptoms (NPS). Method We tested 290 patients with dementia living in nine nursing homes throughout the Netherlands in a longitudinal study. The measurements were repeated every 6months over 2years. We studied the change in NPS and AP use and their effect on QoL over time in two separate generalized estimating equations. We assessed QoL and NPS using the Qualidem questionnaire and the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), respectively. Results Antipsychotic prescriptions did not significantly change participant QoL, whereas NPI-NH total score changes consistently predicted changes in QoL. According to the Qualidem, the development of QoL in patients who chronically used APs did not differ from AP-free patients, except on the restless tense behavior subscale. AP-free patients' restless tense behavior improved compared with patients who chronically used APs, who showed a slight deterioration in these symptoms; however, this effect did not significantly influence total QoL. Conclusion Antipsychotic use does not necessarily have detrimental effects on the QoL of patients with dementia; rather, NPS consistently and negatively affects QoL. The use of APs to treat NPS is justified when used carefully (i.e., their benefits and side effects should be monitored). Copyright (c) 2012 John Wiley & Sons, Ltd.

Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure-orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

Since the original data from the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated that nonsurgical therapy could achieve survival rates comparable to total laryngectomy in selected cases, there has been a progressive increase in employment of nonsurgical therapy for the management of advanced laryngeal cancer. Both neoadjuvant chemotherapy followed by conventionally fractionated or hyperfractioned radiotherapy for chemotherapy responders, or simultaneously administered chemoradiation has resulted in a significant number of patients who achieved cure while preserving their larynges. Nevertheless, combined chemotherapy and external beam radiation is associated with a variety of acute and chronic sequelae that can have a debilitating impact on function and quality of life. Although no therapeutic option is without risk, the decision regarding the modality of therapy for a patient with advanced laryngeal cancer should prompt a careful review of the current surgical techniques available for treatment. Data on quality of life and aging, as well as advances in minimally invasive surgical techniques, are available today that were not available at the time of the Veterans study. Selection of optimal therapy is often complex and raises the question whether the pendulum may have swung too far in the direction of nonsurgical therapy for advanced laryngeal cancer. This article reviews the current options available for a patient with advanced laryngeal cancer and discusses the impact of therapy. (c) 2007 Wiley Periodicals, Inc.

Randomized controlled trials (RCTs) are the golden standard for the assessment of drug efficacy. Little is known about the add-on value of observational studies in heart failure (HF). We aimed to assess the contribution of observational studies to actual knowledge regarding the effectiveness of angiotensin-converting enzyme inhibitors (ACEI), and beta-blockers (BB) in HF.Observational studies that assessed the effectiveness of ACEI and BB in HF were identified by searching Medline, Embase, Cochrane Database (1990-2005) and the bibliographies of published articles. Cohort, case-control and time-series analysis studies were considered for inclusion. Studies with A total of 23 cohort studies met the inclusion criteria. Studies of ACEI and BB showed a decrease in mortality with drug use in elderly patients with a broad range of ejection fraction (EF), and in those with depressed EF. Additionally, they showed a decrease in mortality in patients with renal insufficiency. The effect of ACEI and BB in HF with preserved EF was not clear, although last evidence suggests a potential benefit. Low-dose ACEI and BB may have beneficial effects. Target doses of ACEI seemed superior to low doses, but there was no clear dose-response relationship.Observational studies in HF validate the effectiveness of ACEI and BB in populations underrepresented or excluded from RCTs. Observational studies of drug effectiveness provide relevant additional information for clinical practice.

Aims Randomized controlled trials (RCTs) are the golden standard for the assessment of drug efficacy. Little is known about the add-on value of observational studies in heart failure (HF). We aimed to assess the contribution of observational studies to actual knowledge regarding the effectiveness of angiotensin-converting enzyme inhibitors (ACEI), and β-blockers (BB) in HF. Methods Observational studies that assessed the effectiveness of ACEI and BB in HF were identified by searching Medline, Embase, Cochrane Database (1990–2005) and the bibliographies of published articles. Cohort, case–control and time-series analysis studies were considered for inclusion. Studies with

Aims The effects of β-blockers in daily practice patients with advanced chronic heart failure (CHF) and a broad range of ejection fraction (EF) are not well established. We aimed to assess, first, the association between β-blocker prescription at discharge and mortality in a cohort of patients with advanced CHF, and second, whether this association is modified by the age of the patient. Methods Patients diagnosed with advanced CHF (n = 625) were prospectively followed after discharge from the Cardiology Department. The mean age was 76 years, 53% male, mean EF 42 ± 16%. Overall, 308 (49%) patients had a β-blocker prescribed at discharge, 140 (22%) low-dose and 168 (27%) high-dose therapy. We used multivariate Cox analysis to assess the association between β-blocker use at discharge and mortality. Results After a mean follow-up of 22 months, 117 (27%) patients died. Prescription of a β-blocker was associated with a 45% relative risk reduction (hazard ratio 0.55, 95% confidence interval 0.39, 0.78). The relative risk reduction was similar with low and high doses of β-blockers (42% and 49%). However, the relative risk reduction was higher in younger than in older patients (P = 0.006). In patients ≤75 years old prescription of a β-blocker was associated with 71% risk reduction, whereas in patients >75 years old it was associated with 21% risk reduction. Conclusions In this daily practice cohort of patients with advanced CHF, prescription of a β-blocker was associated with significant mortality reduction. However, the beneficial effects of β-blockers appear to be greater in younger patients.

Background: The effects of beta-blockers in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) are not well established.Aims: To assess the association between beta-blocker prescription at discharge and mortality in a cohort of patients with advanced HF and preserved LVEF.Methods and results: We prospectively studied a cohort of 443 patients with advanced HF and preserved LVEF (LVEF >= 40%). Mean age was 78 years, 56% female, 33% NYHA class IV. Overall, 227 patients (51%) had a beta-blocker prescribed at discharge. Mean duration of follow-up was 25 ( 18) months. Death (all cause) occurred in 40 patients (17.6%) who were receiving a beta-blocker at discharge and 73 patients (33.8%) who were not on a beta-blocker. In multivariate Cox analysis, including adjustment for propensity score, prescription of a beta-blocker remained associated with a 43% relative mortality risk reduction (HR 0.57, 95% CI 0.37 to 0.88, p=0.01).Conclusions: In this cohort of patients with advanced HF and preserved LVEF, prescription of a beta-blocker was associated with a significant mortality reduction. This beneficial effect of beta-blocker use needs to be further confirmed in prospective, randomised clinical trials. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Since the original data from the Department of Veterans Affairs Laryngeal Cancer Study Group demonstrated that nonsurgical therapy could achieve survival rates comparable to total laryngectomy in selected cases, there has been a progressive increase in employment of nonsurgical therapy for the management of advanced laryngeal cancer. Both neoadjuvant chemotherapy followed by conventionally fractionated or hyperfractioned radiotherapy for chemotherapy responders, or simultaneously administered chemoradiation has resulted in a significant number of patients who achieved cure while preserving their larynges. Nevertheless, combined chemotherapy and external beam radiation is associated with a variety of acute and chronic sequelae that can have a debilitating impact on function and quality of life. Although no therapeutic option is without risk, the decision regarding the modality of therapy for a patient with advanced laryngeal cancer should prompt a careful review of the current surgical techniques available for treatment. Data on quality of life and aging, as well as advances in minimally invasive surgical techniques, are available today that were not available at the time of the Veterans study. Selection of optimal therapy is often complex and raises the question whether the pendulum may have swung too far in the direction of nonsurgical therapy for advanced laryngeal cancer. This article reviews the current options available for a patient with advanced laryngeal cancer and discusses the impact of therapy. (c) 2007 Wiley Periodicals, Inc.

Diagnostic cytogenetic abnormalities are considered important prognostic factors in patients with acute myeloid leukaemia (AML). However, the prognostic assessments have mainly been derived from patients with AML aged

Background: Several randomised studies of heart failure (HF) management programmes in the United States, Australia and Europe have shown a considerable reduction in hospitalisation rates for HE In this article, a comprehensive review of these studies will be provided and their applicability to countries, with a primary care-based healthcare system, will be discussed. In addition, the design of the Deventer-Alkmaar HF Project (DEAL-HF), a randomised study of the effect of a nurse and physician-directed intervention over 1 year in The Netherlands, will also be presented. Aim: To discuss the applicability of the results of available studies on heart failure management programmes to countries with well-structured primary care facilities and to determine whether additional trials should be conducted in these countries. Methods: We performed a literature search in PubMed. In a review of the available studies, essential methodological aspects, in particular, the population involved, the sample size, follow-up period, setting, type of intervention, and the outcome parameters, are discussed critically. Also, the applicability of these studies to countries with a primary care-based healthcare system and easy access to medical care is evaluated. Conclusion: Applicability of the results of the available studies on the efficacy of heart failure management programmes to countries with a primary care-based health care system is doubtful. An efficacy trial in a country with a well-established primary care-based healthcare system, such as The Netherlands, is due to report soon (DEAL-HF). (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

A heart failure team that treats heart failure patients often faces the challenge of managing multiple conditions requiring multiple medications and life style changes in an older patient group. A multidisciplinary team approach can optimally diagnose, carefully review and prescribe treatment, and educate and counsel patients and their families about medication use and life style changes. In this paper the possible role of the pharmacist, dietician, physical therapist, psychologist, primary care provider and social worker in heart failure management is discussed. (C) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

A heart failure team that treats heart failure patients often faces the challenge of managing multiple conditions requiring multiple medications and life style changes in an older patient group. A multidisciplinary team approach can optimally diagnose, carefully review and prescribe treatment, and educate and counsel patients and their families about medication use and life style changes. In this paper the possible role of the pharmacist, dietician, physical therapist, psychologist, primary care provider and social worker in heart failure management is discussed. (C) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Background: Because of the improvement of the pharmacological and non-pharmacological treatment in heart failure (HF) patients, the HF related therapeutic regimen is becoming more complicated. Non-compliance with this regimen can result in worsening HF symptoms, sometimes leading to hospitalisation. Aims: The aims of this systematic literature review are (1) to describe the consequences of noncompliance in HF patients; (2) to summarise the degree of compliance in the various aspects of the therapeutic regimen; and (3) to review interventions that are recommended to improve compliance in HF patients. Methods: A literature search of the MEDLINE and CINAHL database from 1988 to June 2003 was performed. Studies on compliance with life style recommendations according to the HF Guidelines of the European Society of Cardiology and the American Heart Association/American College of Cardiology were included. Conclusion: Noncompliance with medication and other lifestyle recommendations is a major problem in patients with HE Evidence based interventions to improve compliance in patients with HF are scarce. Interventions that can increase compliance and prevent HF related readmissions in order to improve the quality of life of patients with HF need to be developed and tested. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

OBJECTIVE To analyse the impact of patient age on survival after radical cystectomy (RC). PATIENTS AND METHODS After ethics review board approval, two databases of patients with bladder cancer (BC) undergoing RC at the University Heath Network, Toronto, Canada (1992-2008) and the University of Turku, Turku, Finland (1986-2005) were retrospectively analysed. A total of 605 patients who underwent this procedure between June 1985 and March 2010 were included. Patients were divided into four age groups: = 80 years. Demographic, clinical and pathological data were compared, as well as recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OAS) rates. RESULTS Compared with younger patients (age = 80 years) had higher American Society of Anesthesiologists scores (P < 0.001), a greater number of lymph nodes removed during surgical dissection (P < 0.001), and underwent less adjuvant treatment (P < 0.001). Choice of urinary diversion differed among the groups, with ileal conduit being used for all patients >= 80 years (P < 0.001). No differences were noted between age groups with respect to RFS (P = 0.3), DSS (P = 0.4) or OAS (P = 0.4). CONCLUSION Although RC is an operation with significant morbidity, it is a viable treatment option for carefully selected elderly patients. Senior patients (>= 80 years) should not be denied RC if they are deemed fit to undergo surgery. Senior adults do not suffer from adverse histopathological features as compared with younger patients.

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m2/d) and P (60 mg/m2/d) for 4 d every 6 wk (n = 62) or MP and thalidomide (100 mg/d) continuously (n = 60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P = 0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P = 0.655; DFS 21.0 vs. 14.0 months, P = 0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P = 0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n = 8, 14.0%) than in the MPT arm (n = 2, 3.4%; P = 0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P = 0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation. ERKİM İlaç A.Ş. Türk Bilimler Akademisi