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IntroductionWorldwide, polypharmacy and medication appropriateness-related outcomes (MARO) are growing public health concerns associated with potentially inappropriate prescribing, adverse health effects, and avoidable costs to health systems. Continuity of care (COC) is a cornerstone of high-quality care that has been shown to improve patient-relevant outcomes. However, the relationship between COC and polypharmacy/MARO has not been systematically explored.ObjectiveThe aim of this systematic review was to investigate the operationalization of COC, polypharmacy, and MARO as well as the relationship between COC and polypharmacy/MARO.MethodsWe performed a systematic literature search in PubMed, Embase, and CINAHL. Quantitative observational studies investigating the associations between COC and polypharmacy and/or COC and MARO by applying multivariate regression analysis techniques were eligible. Qualitative or experimental studies were not included. Information on the definition and operationalization of COC, polypharmacy, and MARO and reported associations was extracted. COC measures were assigned to the relational, informational, or management dimension of COC and further classified as objective standard, objective non-standard, or subjective. Risk of bias was assessed by using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.ResultsTwenty-seven studies were included. Overall, substantial differences existed in terms of the COC dimensions and related COC measures. Relational COC was investigated in each study, while informational and management COC were only covered among three studies. The most frequent type of COC measure was objective non-standard (n = 16), followed by objective standard (n = 11) and subjective measures (n = 3). The majority of studies indicated that COC is strongly associated with both polypharmacy and MARO, such as potentially inappropriate medication (PIM), potentially inappropriate drug combination (PIDC), drug-drug interaction (DDI), adverse drug events (ADE), unnecessary drug use, duplicated medication, and overdose. More than half of the included studies (n = 15) had a low risk of bias, while five studies had an intermediate and seven studies a high risk of bias.ConclusionsDifferences regarding the methodological quality of included studies as well as the heterogeneity in terms of the operationalization and measurement of COC, polypharmacy, and MARO need to be considered when interpreting the results. Yet, our findings suggest that optimizing COC may be helpful in reducing polypharmacy and MARO. Therefore, COC should be acknowledged as an important risk factor for polypharmacy and MARO, and the importance of COC should be considered when designing future interventions targeting these outcomes.

INTRODUCTION: Worldwide, polypharmacy and medication appropriateness-related outcomes (MARO) are growing public health concerns associated with potentially inappropriate prescribing, adverse health effects, and avoidable costs to health systems. Continuity of care (COC) is a cornerstone of high-quality care that has been shown to improve patient-relevant outcomes. However, the relationship between COC and polypharmacy/MARO has not been systematically explored. OBJECTIVE: The aim of this systematic review was to investigate the operationalization of COC, polypharmacy, and MARO as well as the relationship between COC and polypharmacy/MARO. METHODS: We performed a systematic literature search in PubMed, Embase, and CINAHL. Quantitative observational studies investigating the associations between COC and polypharmacy and/or COC and MARO by applying multivariate regression analysis techniques were eligible. Qualitative or experimental studies were not included. Information on the definition and operationalization of COC, polypharmacy, and MARO and reported associations was extracted. COC measures were assigned to the relational, informational, or management dimension of COC and further classified as objective standard, objective non-standard, or subjective. Risk of bias was assessed by using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Twenty-seven studies were included. Overall, substantial differences existed in terms of the COC dimensions and related COC measures. Relational COC was investigated in each study, while informational and management COC were only covered among three studies. The most frequent type of COC measure was objective non-standard (n = 16), followed by objective standard (n = 11) and subjective measures (n = 3). The majority of studies indicated that COC is strongly associated with both polypharmacy and MARO, such as potentially inappropriate medication (PIM), potentially inappropriate drug combination (PIDC), drug-drug interaction (DDI), adverse drug events (ADE), unnecessary drug use, duplicated medication, and overdose. More than half of the included studies (n = 15) had a low risk of bias, while five studies had an intermediate and seven studies a high risk of bias. CONCLUSIONS: Differences regarding the methodological quality of included studies as well as the heterogeneity in terms of the operationalization and measurement of COC, polypharmacy, and MARO need to be considered when interpreting the results. Yet, our findings suggest that optimizing COC may be helpful in reducing polypharmacy and MARO. Therefore, COC should be acknowledged as an important risk factor for polypharmacy and MARO, and the importance of COC should be considered when designing future interventions targeting these outcomes. ispartof: DRUGS & AGING vol:40 issue:6 pages:473-497 ispartof: location:New Zealand status: published

In this national lung cancer audit of inoperable NSCLC patients, acute toxicity and 3-month mortality of curative chemoradiation was analyzed. Another important question was whether concurrent chemoradiation for elderly stage III NSCLC patients is safe. The results showed that 3-month toxicity was significantly higher in patients treated with concurrent chemoradiation, higher TNM stage IIIC and poor performance (WHO >= 2) patients. Introduction: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicit y and 3-month mortalit y of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. Methods: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy. Results: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhema-tological 3-month toxicity (CTCAE grade >3 or radiation pneumonitis grade >2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO >2 (P = .006), and TNM IIIC (P = .031). The multivari-able analysis for acute toxicity was significant for cCRT (P = .015), WHO >2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO >2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. Conclusion: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs.17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO >2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.

Background: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. Objectives: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. Methods: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. Results: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people’s skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. Conclusions: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.

Supportive care (SC) is a multidimensional and person-centred approach to managing advanced CKD that engages the person and their caregivers in shared decision making from the outset. Rather than focusing on disease-specific therapies, SC is a collection of adjuvant interventions and adaptations to conventional treatments that can be used to improve the individual's quality of life. Recognizing that frailty, multi-morbidity and polypharmacy are more common among older people with advanced chronic kidney disease (CKD) and that people in this group tend to prioritize quality of life over survival as a goal of care, SC represents an important adjunct to disease-specific therapies in CKD management. This review provides an overview of SC in the older person with advanced CKD.Lay Summary Older people with advanced chronic kidney disease (CKD) are more likely to experience frailty and multiple other medical problems (comorbidity). This can result in impaired quality of life and reduced survival compared with younger adults with the same diagnosis. The benefits to be derived from kidney-specific treatments such as dialysis and transplantation are also less well-defined in older adults. Supportive care (SC) involves honest communication with the person about their disease, the treatments available to them and prognosis. Through shared decision making, the person and their doctor will try determine what is important to the person and address those aspects of disease that are contributing most to the person's suffering now, while also making plans for the future. This article provides an overview of SC principles in the older adult with advanced CKD.

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

Aim Optimal dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) intends to balance ischemic and bleeding risks. Various DAPT de-escalation strategies, defined as switching from a full-dose potent to a reduced dose or less potent P2Y12 inhibitor, have been evaluated in several ACS-PCI trials. We aimed to compare DAPT de-escalation to standard DAPT with full-dose potent P2Y12 inhibitors in ACS patients who underwent PCI. Methods and results PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials. Aspirin monotherapy trials were excluded. Five randomized trials (n = 10 779 patients) that assigned DAPT de-escalation (genetically guided to clopidogrel n = 1242; platelet function guided to clopidogrel n = 1304; unguided to clopidogrel n = 1672; unguided to lower dose n = 1170) vs. standard DAPT (control group n = 5391) were included in this analysis. DAPT de-escalation was associated with a significant reduction in Bleeding Academic Research Consortium ≥2 bleeding (HR 0.57, 95% CI 0.42–0.78; I2 = 77%) as well as major adverse cardiac events, represented in most trials by the composite of cardiovascular mortality, myocardial infarction, stent thrombosis, and stroke (HR 0.77, 95% CI 0.62–0.96; I2 = 0%). Notwithstanding the limited power, consistency was noted across various de-escalation strategies. Conclusion De-escalation of DAPT after PCI for ACS, both unguided and guided by genetic or platelet function testing (PFT), was associated with lower rates of clinically relevant bleeding and ischemic events as compared to standard DAPT with potent P2Y12 inhibitors based on five open-label RCTs reviewed.

Background Acute low energy pubic rami fractures in the elderly receive primarily conservative treatment. There is debate to what extent posterior ring involvement, which is detected superiorly by CT compared to X-ray, has an impact on outcome and may require modified treatment. We want to demonstrate if posterior ring involvement has an influence on different types of outcome in primarily conservatively treated acute FFP, questioning the usefulness of early CT. Additionally we analysed the early fracture pattern in cases where conservative treatment failed with need for secondary surgery. Methods A retrospective cohort study of 155 consecutive patients, recruited between 2009 and 2016, aged over 65 years diagnosed with an acute LE-PFr on X-ray at the emergency department of a single, level-one trauma centre and receiving an early CT. A set of outcome parameters was compared between patients with an isolated pubic rami fracture (CTia) and patients who had a combined posterior pelvic ring fracture (CTcp). Results There were 155 patients of whom 85.2% were female with a mean age of 83 years. 76.8% of patients living at home returned home and 15.5% moved to a nursing home. Mortality rate during hospitalisation was 6.4% and 14.8% at one year post-trauma. Secondary fracture displacement occurred in 22.6%. Secondary surgery was performed in 6 cases (3.9%). Median hospitalisation length of stay was 21 days (range 0 to 112 days). There was no significant association between the subgroups and change in residential status (p = 0.65), complications during hospitalisation (p = 0.75), mortality rate during admission (p = 0.75) and at 1 year (p = 0.88), readmission within 30 days (p = 0.46) and need for secondary surgery (p = 0.2). There was a significant increased median length of stay (p = 0.011) and rate of secondary displacement (p = 0.015) in subgroup CTcp. Secondary displacement had no impact on in-hospital complications (p = 0.7) nor mortality rate during admission (p = 0.79) or at 1 year (0.77). Early CT in patients who underwent secondary surgery showed stable B2.1 lesions in 4 of 6 cases. Conclusions Our data suggest that early CT in patients with conservatively treated acute LE-PFr in order to detect posterior lesions, has limited value in predicting failure of conservative treatment.

The rise in the number of people aged 65 years and older living with inflammatory rheumatic diseases such as rheumatoid arthritis is causing considerable challenges for clinicians. As patients get older, they are at an increased risk of multiple chronic diseases, a situation termed multimorbidity. Multimorbidity inevitably drives polypharmacy, where by a patient requires treatment with multiple medications. In addition, advancing age, multimorbidity and polypharmacy all place a patient at an increased risk of developing geriatric syndromes, which are clinical conditions in older people that do not fit into disease categories and include malnutrition, sarcopenia and frailty. Geriatric syndromes further increase the risk of adverse outcomes, including the accrual of additional morbidity, nursing home admission and mortality. Patients with inflammatory rheumatic diseases are especially prone to developing geriatric syndromes. Some predisposing risk factors for geriatric syndromes, such as joint swelling and functional limitations, are also inherent to rheumatic inflammatory disease itself. The frequent coexistence of multimorbidity, polypharmacy and geriatric syndromes in this patient group requires individually tailored interventions to preserve patient independence and overall functioning. To prepare for the changing demography, rheumatologists should gain more insight into the implications of multimorbidity, polypharmacy and geriatric syndromes for the management of older patients with inflammatory rheumatic diseases.In this Review, the authors discuss the challenges of multimorbidity, polypharmacy and geriatric syndromes in older patients with inflammatory rheumatic diseases. They note that individually tailored interventions are needed in this patient group in order to preserve patient independence and overall functioning.

The rise in the number of people aged 65 years and older living with inflammatory rheumatic diseases such as rheumatoid arthritis is causing considerable challenges for clinicians. As patients get older, they are at an increased risk of multiple chronic diseases, a situation termed multimorbidity. Multimorbidity inevitably drives polypharmacy, where by a patient requires treatment with multiple medications. In addition, advancing age, multimorbidity and polypharmacy all place a patient at an increased risk of developing geriatric syndromes, which are clinical conditions in older people that do not fit into disease categories and include malnutrition, sarcopenia and frailty. Geriatric syndromes further increase the risk of adverse outcomes, including the accrual of additional morbidity, nursing home admission and mortality. Patients with inflammatory rheumatic diseases are especially prone to developing geriatric syndromes. Some predisposing risk factors for geriatric syndromes, such as joint swelling and functional limitations, are also inherent to rheumatic inflammatory disease itself. The frequent coexistence of multimorbidity, polypharmacy and geriatric syndromes in this patient group requires individually tailored interventions to preserve patient independence and overall functioning. To prepare for the changing demography, rheumatologists should gain more insight into the implications of multimorbidity, polypharmacy and geriatric syndromes for the management of older patients with inflammatory rheumatic diseases.In this Review, the authors discuss the challenges of multimorbidity, polypharmacy and geriatric syndromes in older patients with inflammatory rheumatic diseases. They note that individually tailored interventions are needed in this patient group in order to preserve patient independence and overall functioning.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to older adults. In contrast to young subjects, it is unclear whether older adults may be vulnerable to cognitive side effects. Serotonin is involved in cognitive functions (e.g. memory). It is of great importance to examine the effects of SSRIs on memory functioning in older adults.OBJECTIVES: The objective of this systematic literature review is to summarize studies in which the effects of SSRI treatment on all aspects of memory functioning in older adults are investigated.METHODS: PubMed, PsycINFO, CINAHL, and Embase were searched for all studies published until 18th of October 2021. Articles were included if they fulfilled the inclusion criteria as follows: (1) study design is (randomized) controlled trial, cross-sectional, or prospective cohort study; (2) study population consists of older adults (mean age ⩾65 years), or results for this age-group are reported separately; (3) intervention is use of an SSRI; and (4) effects on performance of any memory domain are measured and clearly described.RESULTS: The search yielded 1888 articles, of which 136 were included for the full-text review. Eventually, 40 articles were included. Most studies reported no association between SSRI use and memory functioning. The studies that found a positive association mainly investigated older adults with mental or neurological disorders (e.g. depression or stroke). A few studies found a negative association in the following subgroups: non-responders (depression), patients with frontal brain disease, and women.CONCLUSION: Overall, no consistent negative effects of SSRIs on memory functioning in older adults were found after SSRI treatment. Most studies reported no change in memory functioning after SSRI use. Some studies even showed an improvement in memory performance. Positive effects of SSRIs on memory functioning were especially found in older adults with mental or neurological disorders, such as subjects with depression or stroke.

Anne L Meulenbroek,1 Miriam C Faes,2 Stefanie R van Mil,1 MG Buimer,1 Hans GW de Groot,1 Eelco J Veen,1 Gwan H Ho,1 Leandra JM Boonman-de Winter,3,4 Jolanda de Vries,5,6 Rebecca van Gorkom,1 Fleur Toonders,1 Rene van Alphen,7 Karolien van Overveld,8 Nathalie Verbogt,1 Ewout W Steyerberg,9 Lijckle van der Laan1,10 1Department of Surgery, Amphia Hospital, Breda, the Netherlands; 2Department of Geriatrics, Amphia Hospital, Breda, the Netherlands; 3Department of Scientific Research, Amphia Hospital, Breda, the Netherlands; 4Admiraal de Ruyter Ziekenhuis, Goes, the Netherlands; 5Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands; 6Board, Admiraal de Ruyter Hospital, Goes, the Netherlands; 7Department of Physical Therapy, Amphia Hospital, Breda, the Netherlands; 8Department of Dieticians, Amphia Hospital, Breda, the Netherlands; 9Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, the Netherlands; 10Department of Cardiovascular Science, University Hospitals Leuven, Leuven, BelgiumCorrespondence: Anne L Meulenbroek, Department of Surgery, Amphia Hospital, Molengracht 21, Breda, 4818 CK, the Netherlands, Tel +31 76 595 3157, Fax +31 76 595 3818, Email AMeulenbroek1@amphia.nlObjective: Chronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥ 65 years.Design: A prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program.Methods: Chronic limb threatening ischemia patients ≥ 65 years that require revascularization will participate in the program. This program focuses on optimizing the patient’s overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group.Discussion: This study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient’s preoperative mental and physical condition to prevent postoperative complications, including delirium.Trial: This protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.Keywords: chronic limb threatening ischemia, vascular surgical procedures, delirium, delirium/prevention and control, prehabilitation

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to older adults. In contrast to young subjects, it is unclear whether older adults may be vulnerable to cognitive side effects. Serotonin is involved in cognitive functions (e.g. memory). It is of great importance to examine the effects of SSRIs on memory functioning in older adults. Objectives: The objective of this systematic literature review is to summarize studies in which the effects of SSRI treatment on all aspects of memory functioning in older adults are investigated. Methods: PubMed, PsycINFO, CINAHL, and Embase were searched for all studies published until 18th of October 2021. Articles were included if they fulfilled the inclusion criteria as follows: (1) study design is (randomized) controlled trial, cross-sectional, or prospective cohort study; (2) study population consists of older adults (mean age ⩾65 years), or results for this age-group are reported separately; (3) intervention is use of an SSRI; and (4) effects on performance of any memory domain are measured and clearly described. Results: The search yielded 1888 articles, of which 136 were included for the full-text review. Eventually, 40 articles were included. Most studies reported no association between SSRI use and memory functioning. The studies that found a positive association mainly investigated older adults with mental or neurological disorders (e.g. depression or stroke). A few studies found a negative association in the following subgroups: non-responders (depression), patients with frontal brain disease, and women. Conclusion: Overall, no consistent negative effects of SSRIs on memory functioning in older adults were found after SSRI treatment. Most studies reported no change in memory functioning after SSRI use. Some studies even showed an improvement in memory performance. Positive effects of SSRIs on memory functioning were especially found in older adults with mental or neurological disorders, such as subjects with depression or stroke.

Background Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. Objectives To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. Material and Methods A cohort study was conducted in a Dutch tertiary care hospital including patients aged >= 70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. Results In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index >= 1 discontinued treatment more often. Conclusion All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value.

Background This phase 1b/2 PCYC-1123-CA study evaluated efficacy and safety of the combination of ibrutinib, lenalidomide, and rituximab (iR2 regimen) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem cell transplantation.Methods In phase 2, patients with relapsed/refractory non-germinal centre B-cell-like DLBCL received oral ibrutinib 560 mg once daily and oral lenalidomide 20 mg or 25 mg once daily on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity and intravenous rituximab 375 mg/m2 on Day 1 of Cycles 1-6. The primary endpoint was overall response rate (ORR) in the response-evaluable population (received any study treatment and had >= 1 post-baseline disease assessment). The study was done at 24 academic and community hospitals in Belgium, Germany, United Kingdom, and USA. This study was registered with ClinicalTrials.gov, NCT02077166. Findings Between March 13, 2014 and October 2, 2018, 89 patients were enrolled with a median time on study of 35.0 months. Best ORR in the response-evaluable population (n = 85) was 49% (95% confidence interval [CI], 38-61) across dose cohorts and 53% (95% CI, 39-67) and 44% (95% CI, 26-62) in the 20 mg and 25 mg lenalidomide cohorts, respectively, with complete responses in 24/85 (28%), 17/53 (32%), and 7/32 (22%) patients, respectively. Grade 3/4 adverse events (AEs) occurred in 81/89 patients (91%), most frequently neutropenia (36/89; 40%), maculopapular rash (16/89; 18%), anaemia (12/89; 13%), and diarrhoea (9/89; 10%). Serious adverse events occurred in 57/89 patients (64%). Fatal AEs occurred in 12/89 patients (13%); causes of death were worsening of DLBCL (n = 7), pneumonia (n = 3), sepsis (n = 1), and cardiac arrest (n = 1). Interpretation The most frequent AEs (diarrhoea, neutropenia, fatigue, cough, anaemia, peripheral oedema, and maculopapular rash) were consistent with known safety profiles of the individual drugs. The iR2 regimen demon-strated antitumour activity with durable responses in patients with relapsed/refractory DLBCL.Copyright (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND: The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged METHOD: This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015-31 December 2018). Kaplan-Meier curves and Cox proportional hazards models were used to assess OS.RESULTS: Overall, 10,298 patients were included, of whom 1551 (15%) were CONCLUSION: Patients with PDAC

Background: Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC.Methods: A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model.Results: Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57-0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64-0.97) versus 0.56 (95% CI: 0.46-0.69; p < 0.001), respectively.Conclusions: This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.

BackgroundOlder patients (> 65 yr) suffering from overactive bladder (OAB) are more likely to have functional impairment and comorbidity than those without OAB. This article reviews available published studies and discusses how fesoterodine might meet the specific needs of the older OAB patient.MethodsA comprehensive literature search was undertaken in order to evaluate fesoterodine safety in older OAB patients.ResultsFesoterodine offers flexible dosing, allowing the clinician to balance risk and benefits according to the symptoms and preferences of the patient. Its balanced affinity for M2 and M3 muscarinic receptors may lead to its benefit on OAB symptoms. Its active metabolite is a P-gp substrate that is actively transported from the central nervous system (CNS), potentially avoiding adverse CNS effects. Fesoterodine can be used in mild or moderate hepatic or renal insufficiency and no dose adjustment is routinely required. Fesoterodine's benefit has been demonstrated in multiple clinical trials in older and medically vulnerable patients. Fesoterodine was rated as "beneficial" in the LUTS-FORTA classification due to its efficiency and tolerability in older patients.ConclusionHere, the use of fesoterodine in older and vulnerable patients is summarized given the need to approach pharmacotherapy for OAB differently in older adults.

Aims and objectives The holistic care dependency concept can be applied to gain comprehensive insights into individuals' care needs in the end-of-life (EoL) phase. This study was carried out to measure and characterise the "care dependency" phenomenon in this phase and to obtain deeper knowledge about this phenomenon. Background The end of a human life is often characterised by a physical decline, often implying that a high amount of care is needed. Non-malignant diseases can develop unpredictably; therefore, it is difficult to detect the onset of the EoL phase. Design Data were collected in a cross-sectional multicentre study, using the Austrian Nursing Quality Measurement 2.0. Methods Descriptive and multivariate statistical methods were used. Care dependency was measured with the Care Dependency Scale (CDS). The study follows the STROBE guideline. Results Ten per cent (n = 389) of the sample (N = 3589) were allocated to "a pathway for management of patients at the end of life." The patients and residents in the EoL phase are significantly older and more often diagnosed with dementia, and circulatory system and musculoskeletal system diseases. Of these patients, 60% were care dependent completely or to a great extent. Dementia and age represent main influencing factors that affect the degree of care dependency at the end of life. Conclusion Our results show that the "typical" EoL patient or resident is female, old and affected by dementia and/or circulatory system diseases. Dementia and age were identified as main factors that contribute to very high care dependency. Relevance to clinical practice The measurement of care dependency may support the identification of special care needs in the EoL phase. Gaining deeper knowledge about the care dependency phenomenon can also help healthcare staff better understand the needs of patients with non-malignant conditions in their last phase of life.

Purpose: To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting.Methods: Members of GEC ESTRO with expertise in rectal CXB issued consensus-based recommendations for CXB based on literature review and clinical experience. Levels of evidence according to the Oxford Centre for Evidence based medicine guidance are presented where possible.Results: The GEC ESTRO ACROP consensus recommendations support the use of CXB to increase the chances of clinical complete remission and cure for patients who are elderly with high surgical risk, surgically unfit or refusing surgery. For palliative treatment, the use of CXB is recommended for symptomatic relief and disease control. The use of CXB in an organ-preservation setting in surgically fit patients is recommended within the setting of a clinical trial or registry.Conclusions: The GEC ESTRO ACROP recommendations for CXB are provided. Recommendations towards standardisation of reporting and prescription are given. Practitioners are encouraged to follow these recommendations and to develop further clinical trials to examine this treatment modality and increase the evidence base for its use. The routine collection of outcomes both clinical and patient-reported is also encouraged.

Background Vascular surgery is considered a risk factor for the development of postoperative delirium (POD). In this systematic review we provide a report on the incidence and risk-factors of POD after vascular surgery. Methods A systematic literature search was conducted using Pubmed with the MeSH terms and key words “delirium” or “confusion”, “vascular surgery procedures” and “risk factors or “risk assessment”. Studies were selected for review after meeting the following inclusion criteria: vascular surgery, POD diagnosed using validated screening tools, and DSM-derived criteria to assess delirium. A meta-analysis was performed for each endpoint if at least two studies could be combined. Results Sixteen articles met the abovementioned criteria. The incidence of delirium ranged from 5% to 39%. Various preoperative risk factors were identified that is, age (Random MD 3.96, CI 2.57–5.35), hypertension (Fixed OR 1.30, CI 1.05–1.59), diabetes mellitus (Random OR 2.15, CI 1.30–3.56), hearing impairment (Fixed OR 1.89, CI 1.28–2.81), history of cerebrovascular incident or transient ischemic attack (Fixed OR 2.20, CI 1.68–2.88), renal failure (Fixed OR 1.61, CI 1.19–2.17), and pre-operative low haemoglobin level (fixed MD -0.76, CI -1.04 to -0.47). Intra-operative risk factors were duration of surgery (Random MD 15.68; CI 2.79–28.57), open aneurysm repair (Fixed OR 4.99, CI 3.10–8.03), aortic cross clamping time (fixed MD 7.99, CI 2.56–13.42), amputation surgery (random OR 3.77, CI 2.13–6.67), emergency surgery (Fixed OR 4.84, CI 2.81–8.32) and total blood loss (Random MD 496.5, CI 84.51–908.44) and need for blood transfusion (Random OR 3.72, CI 1.57–8.80). Regional anesthesia on the other hand, had a protective effect. Delirium was associated with longer ICU and hospital length of stay, and more frequent discharge to a care facility. Conclusions POD after vascular surgery is a frequent complication and effect-size pooling supports the concept that delirium is a heterogeneous disorder. The risk factors identified can be used to either design a validated risk factor model or individual preventive strategies for high-risk patients.

Background: Vascular surgery is considered a risk factor for the development of postoperative delirium (POD). In this systematic review we provide a report on the incidence and risk-factors of POD after vascular surgery.Methods: A systematic literature search was conducted using Pubmed with the MeSH terms and key words "delirium" or "confusion", "vascular surgery procedures" and "risk factors or "risk assessment". Studies were selected for review after meeting the following inclusion cr iter ia: vascular surgery, POD diagnosed using validated screening tools, and DSM-derived criteria to assess delirium. A meta-analysis was performed for each endpoint if at least two studies could be combined.Results: Sixteen articles met the abovementioned cr iter ia. The incidence of delir ium ranged from 5% to 39%. Various preoperative risk factors were identified that is, age (Random MD 3.96, CI 2.57-5.35), hypertension (Fixed OR 1.30, CI 1.05-1.59), diabetes mellitus (Random OR 2.15, CI 1.30-3.56), hearing impairment (Fixed OR 1.89, CI 1.28-2.81), history of cerebrovascular incident or transient ischemic attack (Fixed OR 2.20, CI 1.68-2.88), renal failure (Fixed OR 1.61, CI 1.19-2.17), and pre-operative low haemoglobin level (fixed MD-0.76, CI-1.04 to-0.47). Intra-operative risk factors were duration of surgery (Random MD 15.68; CI 2.79-28.57), open aneurysm repair (Fixed OR 4.99, CI 3.10-8.03), aortic cross clamping time (fixed MD 7.99, CI 2.56-13.42), amputation surgery (random OR 3.77, CI 2.13-6.67), emergency surgery (Fixed OR 4.84, CI 2.81-8.32) and total blood loss (Random MD 496.5, CI 84.51-908.44) and need for blood transfusion (Random OR 3.72, CI 1.57-8.80). Regional anesthesia on the other hand, had a protective effect. Delirium was associated with longer ICU and hospital length of stay, and more frequent discharge to a care facility.Conclusions: POD after vascular surgery is a frequent complication and effect-size pooling supports the concept that delirium is a heterogeneous disorder. The risk factors identified can be used to either design a validated risk factor model or individual preventive strategies for high-risk patients.

Background: Literature suggests that different risks of mortality could influence physicians in prescribing or not anticoagulants in older patients with atrial fibrillation (AF). The Multidimensional Prognostic Index (MPI) can be considered a tool for the detection of multidimensional frailty. The aim of this cross-sectional study was to evaluate whether prescription patterns of oral anticoagulants exist, based on MPI values. Methods: Older hospitalised patients (age >= 65 years) with non-valvular AF were included across 24 European centres. MPI was calculated using validated and standardised tools derived from a comprehensive geriatric assessment. Other functional and clinical information were collected to calculate indexes specific for haemorrhagic and thromboembolic risk in AF. Results: Altogether, 2,012 participants affected by AF (mean age was 83.2 +/- 7.5, range: 65-104 years), with a higher presence of women (57.0%), were included. Overall, 440 took vitamin K antagonists VKAs (22.0%), 667 (33.4%) direct oral anticoagulants (DOACs), whilst 44.6% did not take any anticoagulant treatment. Prescription of anticoagulants was associated with MPI values, with people taking anticoagulants having lower mean MPI values. Anticoagulant therapy was not used in 53.1% of the group with the highest risk of mortality, compared with 32.3% of those in the group with the lowest mortality risk. People with higher scores in MPI were less frequently treated with anticoagulant therapy, after adjusting for several potential confounders. Conclusions: The EURopean study of Older Subjects with Atrial Fibrillation (EUROSAF) suggested that almost half of the older persons with AF do not receive anticoagulants and that MPI is an important determinant in prescribing or not anticoagulants.

Background Both loop diuretics (LDs) and congestion have been related to worse heart failure (HF) outcome. The relationship between the cause and effect is unknown. The aim of this study was to investigate the interaction between congestion, diuretic use and HF outcome.Methods Six hundred and twenty-two chronic HF patients from TIME-CHF were studied. Congestion was measured by means of a clinical congestion index (CCI). Loop diuretic dose was considered at baseline and month 6. Treatment intensification was defined as the increase in LD dose over 6 months or loop diuretic and thiazide or thiazide-like diuretic co-administration. The end-points were survival and HF hospitalisation-free survival.Results High-LD dose at baseline and month 6 (>= 80 mg of furosemide per day) was not identified as an independent predictor of outcome. CCI at baseline remained independently associated with impaired survival [hazard ratio (HR) 1.34, (95% confidence interval) (95% CI) (1.20-1.50), p Conclusion Intensification of pharmacological decongestion but not the actual LD dose was related to poor outcome in chronic HF. If treatment intensification translated into clinical decongestion, outcome was better than in case of persistent or worsening congestion.[GRAPHICS].

BACKGROUND: For well-selected patients and procedures, laparoscopic liver resection (LLR) has become the gold standard for the treatment of colorectal liver metastases (CRLM) when performed in specialized centers. However, little is currently known concerning patient-related and peri-operative factors that could play a role in survival outcomes associated with LLR for CRLM. AIM: To provide an extensive summary of reported outcomes and prognostic factors associated with LLR for CRLM. METHODS: A systematic search was performed in PubMed, EMBASE, Web of Science and the Cochrane Library using the keywords "colorectal liver metastases", "laparoscopy", "liver resection", "prognostic factors", "outcomes" and "survival". Only publications written in English and published until December 2019 were included. Furthermore, abstracts of which no accompanying full text was published, reviews, case reports, letters, protocols, comments, surveys and animal studies were excluded. All search results were saved to Endnote Online and imported in Rayyan for systematic selection. Data of interest were extracted from the included publications and tabulated for qualitative analysis. RESULTS: Out of 1064 articles retrieved by means of a systematic and grey literature search, 77 were included for qualitative analysis. Seventy-two research papers provided data concerning outcomes of LLR for CRLM. Fourteen papers were eligible for extraction of data concerning prognostic factors affecting survival outcomes. Qualitative analysis of the collected data showed that LLR for CRLM is safe, feasible and provides oncological efficiency. Multiple research groups have reported on the short-term advantages of LLR compared to open procedures. The obtained results accounted for minor LLR, as well as major LLR, simultaneous laparoscopic colorectal and liver resection, LLR of posterosuperior segments, two-stage hepatectomy and repeat LLR for CRLM. Few research groups so far have studied prognostic factors affecting long-term outcomes of LLR for CRLM. CONCLUSION: In experienced hands, LLR for CRLM provides good short- and long-term outcomes, independent of the complexity of the procedure. ispartof: WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY vol:13 issue:7 pages:732-757 ispartof: location:China status: published

We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.

Supportive care (SC) is a multidimensional and person-centred approach to managing advanced CKD that engages the person and their caregivers in shared decision making from the outset. Rather than focusing on disease-specific therapies, SC is a collection of adjuvant interventions and adaptations to conventional treatments that can be used to improve the individual's quality of life. Recognizing that frailty, multi-morbidity and polypharmacy are more common among older people with advanced chronic kidney disease (CKD) and that people in this group tend to prioritize quality of life over survival as a goal of care, SC represents an important adjunct to disease-specific therapies in CKD management. This review provides an overview of SC in the older person with advanced CKD.Lay Summary Older people with advanced chronic kidney disease (CKD) are more likely to experience frailty and multiple other medical problems (comorbidity). This can result in impaired quality of life and reduced survival compared with younger adults with the same diagnosis. The benefits to be derived from kidney-specific treatments such as dialysis and transplantation are also less well-defined in older adults. Supportive care (SC) involves honest communication with the person about their disease, the treatments available to them and prognosis. Through shared decision making, the person and their doctor will try determine what is important to the person and address those aspects of disease that are contributing most to the person's suffering now, while also making plans for the future. This article provides an overview of SC principles in the older adult with advanced CKD.

Introduction: Life expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC). Materials: Patient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged >60 years diagnosed with HNSCC in 1990-1995 and 2010-2015 were compared using chi-square test and relative survival analysis.Results: Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p 1/4 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease.Conclusion: Relative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed.(c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license

International audience; Background: Achieving target doses of angiotensin-converting-enzyme inhibitor/angiotensin-receptor blockers (ACEi/ARB) and beta-blockers in heart failure with reduced ejection fraction (HFrEF) is often underperformed. In BIOlogy Study to TAilored Treatment in chronic heart failure (BIOSTAT-CHF) study, many patients were not up-titrated for which no clear reason was reported. Therefore, we hypothesized that perceived-risk profile might influence treatment optimization.Methods: We studied 2100 patients with HFrEF (LVEF≤40%) to compare the clinical characteristics and adverse events associated with treatment up-titration (after a 3-month titration protocol) between; a) patients not reaching target doses for unclear reason; b) patients not reaching target doses due to symptoms and/or side effects; c) patients reaching target doses.Results: For ACEi/ARB, (a), (b) and (c) was observed in 51.3%, 25.9% and 22.7% of patients, respectively. For beta-blockers, (a), (b) and (c) was observed in 67.5%, 20.2% and 12.3% of patients, respectively. By multinomial logistic regression analysis for ACEi/ARB, patients in group (a) and (b) had lower blood pressure and poorer renal function, and patients in group (a) were older and had lower ejection fraction. For beta-blockers, patients in group (a) and (b) had more severe congestion and lower heart rate. At 9 months, adverse events (i.e., hypotension, bradycardia, renal impairment, and hyperkalemia) occurred similarly among the three groups.Conclusions: Patients in whom clinicians did not give a reason why up-titration was missed were older and had more co-morbidities. Patients in whom up-titration was achieved did not have excess adverse events. However, from these observational findings, the pattern of subsequent adverse events among patients in whom up-titration was missed cannot be determined.

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 Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. Methods and results ABPM data from reflex syncope patients and controls, matched by average 24 h SBP, age, sex, and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and nighttime SBP drops ( Conclusion SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

BACKGROUND: Optimal treatment for locally advanced rectal cancer is neoadjuvant (chemo)radiation followed by radical surgery. This is challenging in the aging population because of frequently concomitant comorbidity. We analyzed whether age below and above 70 years is associated with differences in treatment strategy and outcome in this population-based study.METHODS: Data between 2008 and 2016 were extracted from the Netherlands Cancer Registry with follow-up until 2021. Differences in therapy, referral and outcome were analyzed using χ2 tests, multivariable logistic regression and relative survival analysis.RESULTS: In total, 6524 locally advanced rectal cancer patients were included. A greater proportion of patients CONCLUSION: Elderly patients with locally advanced rectal cancer received less intensive treatment and were less often referred to higher volume hospitals for surgery. Relative survival was good and comparable after optimal treatment in both age groups. Effort is necessary to improve guideline adherence, and multimodal strategies should be tailored to age, comorbidity and performance status.

AIM: The aim of this systematic review is to summarize all available data on the effect of a geriatric assessment in older patients with cancer, for oncologic treatment decisions, the implementation of non-oncologic interventions, patient-doctor communication, and treatment outcome. Additionally, we examined the impact of the type of assessment used. METHODS: Systematic Medline and Embase search for studies on the effect of a geriatric assessment on oncologic treatment decisions, non-oncologic interventions, communication, and outcome. RESULTS: Sixty-five publications from 61 studies were included. After a geriatric assessment, the oncologic treatment plan was altered in a median of 31% of patients (range 7-56%), with highest change rates in studies using a multidisciplinary team evaluation. Non-oncologic interventions were recommended in over 70% of patients, provided that an intervention plan or specific expertise was in place. A geriatric assessment led to more goals-of-care discussions and improved communication. The geriatric assessment also led to lower toxicity/complication rates (most strongly if the assessment outcomes were considered during decision making), improved likelihood of treatment completion, and improved physical functioning and quality of life in the majority of included studies. CONCLUSION: A geriatric assessment can change oncologic treatment plans, leads to non-oncologic interventions, and improve communication about care planning and ageing-related issues. It can decrease toxicity/complications and improve treatment completion and patient-centred outcomes. If multidisciplinary or geriatric input is not available, having a pre-defined non-oncologic intervention plan is important. To maximize the effect on outcomes, the result of the geriatric assessment should be incorporated into oncologic decision-making. ispartof: JOURNAL OF GERIATRIC ONCOLOGY vol:13 issue:6 pages:761-777 ispartof: location:Netherlands status: published

In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients.

Type 2 diabetes (T2D) is a progressive disease, with many individuals eventually requiring basal insulin therapy to maintain glycaemic control. However, there exists considerable therapeutic inertia to the prompt initiation and optimal titration of basal insulin therapy due to barriers that include fear of injections, hypoglycaemia, weight gain, and burdensome regimens. Hypoglycaemia is thought to be a major barrier to optimal glycaemic control and is associated with significant morbidity and mortality. Newer second-generation basal insulin analogues provide comparable glycaemic control with lower risk of hypoglycaemia compared with first-generation basal insulin analogues. The present review article discusses clinical evidence for one such second-generation basal insulin analogue, insulin glargine 300 U/mL (Gla-300), in the context of hypothetical case studies that are representative of individuals who may attend routine clinical practice. These case studies discuss individualised treatment needs for people with T2D who are insulin-naive or pre-treated. Clinical characteristics such as older age, frequent nocturnal hypoglycaemia, and renal impairment, which are known risk factors for hypoglycaemia, are also considered.

Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL (P = 0.066) and fatigue (P = 0.189), and significantly longer TTD in PF (P = 0.028) and HS-VAS (P P = 0.011), PF (P = 0.020), and fatigue (P = 0.004), and a trend in HS-VAS (P = 0.057). Approximately 43%, 35%, 32%, and 18% of patients treated with VEN + AZA, AZA + PBO, VEN + LDAC, or LDAC + PBO, respectively, saw improvements >MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.

Purpose: CD28, CD57, and KLRG1 have been previously identified as markers of T-cell immunosenescence. The impact of immunosenescence on anti-PD(L)-1 (ICI) or platinum-based chemotherapy (PCT) in patients with advanced non–small cell lung cancer (aNSCLC) is unknown. Experimental Design: The percentage of CD28−, CD57+, KLRG1+ among CD8+ T cells [senescent immune phenotype (SIP)] was assessed by flow cytometry on blood from patients with aNSCLC before single-agent ICI (discovery cohort). A SIP cut-off was identified by log-rank maximization method and patients with aNSCLC treated with ICI (validation cohort) or PCT were classified accordingly. Proliferation and functional properties of SIP+ CD8+ T cells were assessed in vitro. Results: In the ICI discovery cohort (N = 37), SIP cut-off was 39.5%, 27% of patients were SIP+. In the ICI validation cohort (N = 46), SIP+ status was found in 28% of patients and significantly correlated with worse objective response rate (ORR; 0% vs. 30%, P = 0.04), median progression-free survival (PFS) [1.8 (95% confidence interval (CI), 1.3-NR) vs. 6.4 (95% CI, 2–19) months, P = 0.009] and median overall survival, OS [2.8 (95% CI, 2.0-NR) vs. 20.8 (95% CI, 6.0-NR) months, P = 0.02]. SIP+ status was significantly associated with circulating specific immunephenotypes, in vitro lower CD8+ T cells proliferation, lower IL2 and higher TNFα and IFNγ production. In the ICI-pooled population (N = 83), SIP+ status did not correlate with any clinical characteristics and it was associated with significantly worse ORR, PFS, and OS. In PCT cohort (N = 61), 11% of patients were SIP+. SIP status did not correlate with outcomes upon PCT. Conclusions: Circulating T-cell immunosenescence is observed in up to 28% of patients with aNSCLC and correlates with lack of benefit from ICI but not from PCT. See related commentary by Salas-Benito et al., p. 374

Background Unlike neighboring countries, the Netherlands does not have a national acute coronary syndrome (ACS) registry to evaluate quality of care. Objective We conducted a pilot registry in two hospitals to assess the prescription of guideline-recommended therapies in Dutch patients with ACS. Methods We included all consecutive patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (n = 1309) admitted to two Dutch percutaneous coronary intervention centers between March 2015 and February 2016. We collected follow-up medication use and reasons for discontinuation at discharge and 1, 6, and 12 months post-discharge. We assessed the use of optimal medical therapy (OMT), defined as the combined prescription of aspirin, P2Y12 inhibitors, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Results OMT prescription was 43.2% at discharge, 60.1% at 1 month, and 28.7% at 12 months. At 1 month, OMT prescription was significantly lower in patients with NSTEMI (51.8 vs. 65.7% for STEMI; p < 0.001). OMT prescription was lower in women (6 months: 55.4 vs. 62.0%, p = 0.036) and in elderly patients. Conclusion In this pilot study that aimed to extend a national Dutch ACS registry to patients with STEMI and NSTEMI, OMT prescription was comparable to that in other local registries, was lower in women and patients with NSTEMI, and decreased with increasing age. Electronic supplementary material The online version of this article (10.1007/s40256-020-00427-9) contains supplementary material, which is available to authorized users.

Background Mortality prediction is critical on long-term kidney replacement therapy (KRT), both for individual treatment decisions and resource planning. Many mortality prediction models already exist, but as a major shortcoming most of them have only been validated internally. This leaves reliability and usefulness of these models in other KRT populations, especially foreign, unknown. Previously two models were constructed for one- and two-year mortality prediction of Finnish patients starting long-term dialysis. These models are here internationally validated in KRT populations of the Dutch NECOSAD Study and the UK Renal Registry (UKRR). Methods We validated the models externally on 2051 NECOSAD patients and on two UKRR patient cohorts (5328 and 45493 patients). We performed multiple imputation for missing data, used c-statistic (AUC) to assess discrimination, and evaluated calibration by plotting average estimated probability of death against observed risk of death. Results Both prediction models performed well in the NECOSAD population (AUC 0.79 for the one-year model and 0.78 for the two-year model). In the UKRR populations, performance was slightly weaker (AUCs: 0.73 and 0.74). These are to be compared to the earlier external validation in a Finnish cohort (AUCs: 0.77 and 0.74). In all tested populations, our models performed better for PD than HD patients. Level of death risk (i.e., calibration) was well estimated by the one-year model in all cohorts but was somewhat overestimated by the two-year model. Conclusions Our prediction models showed good performance not only in the Finnish but in foreign KRT populations as well. Compared to the other existing models, the current models have equal or better performance and fewer variables, thus increasing models’ usability. The models are easily accessible on the web. These results encourage implementing the models into clinical decision-making widely among European KRT populations.

Purpose To assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years. Methods Ninety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed. Results In older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185–12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098–9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248–66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity. Conclusion Older patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

Background: Pre-dialysis and dialysis patients are at risk for drug related problems (DRPs) due to a high incidence of comorbidities. Pharmacist-led medication reviews might reduce the number of DRPs.Objectives: The aim of this study was to evaluate pharmacist-led medication reviews in pre-dialysis and dialysis patients by determining the number and type of DRPs, nephrologist acceptance of pharmacist interventions and time investment.Methods: From September 2017 until December 2018, pharmacist-led medication reviews were performed on pre-dialysis and dialysis patients. DRPs (medication discrepancies, prescribing issues related to drug and dose selection, drug use problems) were identified using the pharmacists' expert opinion and the STOPP/START criteria. Number and type of accepted pharmacist interventions, sustainability of interventions after at least 1 month and time investment were determined. Practical barriers in the process were appraised.Results: One-hundred twenty five patients were reviewed: 37 pre-dialysis and 88 dialysis patients. In 100 (80%) patients 277 medication discrepancies were identified of which 224 (81%) were accepted by the nephrologist. Pharmacists suggested 422 interventions concerning drug or dose selection for 115 patients; 106 interventions were accepted by the nephrologist, which resulted in 60 patients having medication changed. Ninety percent of those changes remained implemented on follow-up after at least 1 month. In 46 (37%) patients, the clinical pharmacist detected DRPs concerning the drug use process and performed patient counseling. The average time investment was 85 min per patient for the clinical pharmacist and 15 min for the nephrologist. Besides time investment, unclear responsibility for medication management due to multiple prescribers was an important barrier in the process and the main reason for nephrologists to reject pharmacist interventions.Conclusion: Pharmacist-led medication reviews in pre-dialysis and dialysis patients led to medication changes in half of the patients. However, efficiency should be improved before adopting pharmacist-led medication reviews into clinical practice.

Objectives: Although the increasing cancer incidence in older patients is widely recognised, older patients remain underrepresented in clinical cancer trials and eHealth studies. The aim of this research is to identify technological and patient-related barriers to inclusion of this population in a clinical eHealth study. Material and Methods: This is a retrospective analysis of a prospective cohort study with older patients (>= 65 years) undergoing cancer-related surgery, who were identified for a perioperative telemonitoring study. Reasons for ineligibility and refusal had been prospectively registered. Characteristics and postoperative outcomes were compared between participants and non-participants. Results: Between May 2018 and March 2020, 151 patients were assessed for eligibility, resulting in 65 participants and 86 non-participants. The main reason for ineligibility was lack of internet access at home (n = 16), while main reasons for refusal were perceived high mental burden (n = 46) and insufficient digital skills (n= 12). Compared with participants, non-participants were significantly older (mean age 75 vs. 73, p = 0.01); more often female (64% vs. 35%, p = 0.00), unmarried (42% vs. 8%, p = 0.01) living alone (38% vs. 19%, p = 0.02); had a higher ASA classification (43% vs. 19%, p = 0.00); often had polypharmacy (67% vs. 43%, p = 0.00); and were more often discharged to skilled nursing facilities (0% vs. 15%, p = 0.00). Conclusion: Our results confirm the underrepresentation of older female patients with little support from a partner and higher comorbidity. We should be aware of technological and patient-related barriers to including older adults with cancer, in order to avoid further dividing patients with low and high digital health literacy. (C) 2020 Elsevier Ltd. All rights reserved.