Cumulative Illness Rating Scale Research Articles

Combined use of the GRACE ACS risk score and comorbidity indices to increase the effectiveness of hospital mortality risk assessment in patients with acute coronary syndrome

To assess the possibilities of using comorbidity indices together with the GRACE (Global Registry of Acute Coronary Events) scale to assess the risk of hospital mortality in acute coronary syndrome (ACS). The registry study included 2,305 patients with ACS. The frequency of coronary angiography was 54.0%, percutaneous coronary intervention (PCI) 26.9%. Hospital mortality with ACS was 4.8%, with myocardial infarction 9.4%. All patients underwent a comorbidity assessment according to the CIRS system (Cumulative Illness Rating Scale), according to the CCI (Charlson Comorbidity Index) and the CDS (Chronic Disease Score) scale, according to their own scale, which is based on the summation of 9 diseases (diabetes mellitus, atrial fibrillation, stroke, arterial hypertension, obesity, peripheral atherosclerosis, thrombocytopenia, anemia, chronic kidney disease). All patients underwent a mortality risk assessment using the GRACE ACS Risk scale. It was found that the CDS and CIRS indices are not associated with the risk of hospital mortality. With CCI3, the frequency of death outcomes increased from 4.1 to 6.1% (2=4.12, p=0.042). With an increase in the severity of comorbidity from minimal (no more than 1 disease) to severe (4 or more diseases) according to its own scale, hospital mortality increased from 1.2 to 7.4% (2=23.8, p0.0001). In contrast to other scales of comorbidity, our own model more efficiently estimates the hospital prognosis both in the conservative treatment group (2=8.0, p=0.018) and in the PCI group (2=28.5, p=0.00001). It was in the PCI subgroup that the comorbidity factors included in their own model made it possible to increase the area under the ROC curve of the GRACE scale from 0.80 (0.740.87) to 0.90 (0.850.95). CCI and its own comorbidity model, but not CDS and CIRS, are associated with the risk of hospital mortality. The model for assessing comorbidity on a 9-point scale, but not CCI, CDS and CIRS, can significantly improve the predictive value of the GRACE scale.

Predictors of "brain fog" 1year after COVID-19 disease.

IntroductionBrain fog has been described up to 1 year after SARS-CoV-2 infection, notwithstanding the underlying mechanisms are still poorly investigated. In this study, we aimed to evaluate the prevalence of cognitive complaints at 1-year follow-up and to identify the factors related to persistent brain fog in COVID-19 patients.MethodsOut of 246 COVID patients, hospitalized from March 1st to May 31st, a sample of 137 patients accepted to be evaluated at 1 year from discharge, through a full clinical, neurological, and psychological examination, including the Montreal Cognitive Assessment (MoCA), impact of event scale-revised (IES-R), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), and fatigue severity scale (FSS). Subjects with prior cognitive impairment and/or psychiatric disorders were excluded.ResultsPatients with cognitive disorders exhibited lower MoCA score (22.9 ± 4.3 vs. 26.3 ± 3.1, p = 0.002) and higher IES-R score (33.7 ± 18.5 vs. 26.4 ± 16.3, p = 0.050), SDS score (40.9 ± 6.5 vs. 35.5 ± 8.6, p = 0.004), and fatigue severity scale score (33.6 ± 16.1 vs. 23.7 ± 12.5, p = 0.001), compared to patients without cognitive complaints. Logistic regression showed a significant correlation between brain fog and the self-rating depression scale values (p = 0.020), adjusted for age (p = 0.445), sex (p = 0.178), premorbid Cumulative Illness Rating Scale (CIRS) (p = 0.288), COVID-19 severity (BCRSS) (p = 0.964), education level (p = 0.784) and MoCA score (p = 0.909).ConclusionsOur study showed depression as the strongest predictor of persistent brain fog, adjusting for demographic and clinical variables. Wider longitudinal studies are warranted to better explain cognitive difficulties after COVID-19.

Characteristics of geriatric rehabilitation inpatients based on their frailty severity and change in frailty severity during admission: RESORT

BackgroundFrailty is prevalent amongst geriatric inpatients and worsens clinical outcomes. Determinants of admission frailty and changes in frailty severity are potential targets for intervention. ObjectiveTo identify characteristics associated with frailty severity at admission and change in frailty severity during geriatric rehabilitation. MethodsThe observational, prospective, longitudinal inception cohort REStORing health of acutely unwell adulTs (RESORT) includes geriatric rehabilitation inpatients. Demographic, medical, nutritional, functional, and psychological characteristics were analysed according to admission Clinical Frailty Scale. Linear and multinomial logistic regression prediction models identified admission characteristics predicting change in frailty severity during rehabilitation. ResultsA total 1716 inpatients (median age [IQR] 83.4 [77.7–88.6] years, 56.4 % females) were included. Poorer admission medical, nutritional, functional, and psychological status was associated with more severe frailty. Cardiac admissions, higher Cumulative Illness Rating Scale, greater number of medications, and better Short Physical Performance Battery at admission predicted improved frailty severity. Admission cognitive impairment, delirium, higher Charlson Comorbidity Index, and Hospital Anxiety and Depression Scale anxiety predicted worsened frailty severity. Explained variation was low. ConclusionsFrailer geriatric rehabilitation inpatients have more complicated disease and impaired nutritional, physical, and psychological markers. Admission cognitive impairment, delirium, comorbidity, and anxiety predict worsening frailty during rehabilitation, and require prompt management.

Resilience is associated with frailty and older age in hospitalised patients

BackgroundLittle is known about resilience in an internal medicine setting. We aimed to assess the relationship between resilience and frailty and other clinical and sociodemographic characteristics in a cohort of prospectively enrolled hospitalised patients.MethodsIn 2017–2019, we consecutively enrolled patients in our internal medicine wards. We selected all patients who filled in the 25-item Connor-Davidson resilience scale (CD-RISC). Mean resilience was evaluated according to baseline demographic (i.e., age, sex, marital and socioeconomic status) and clinical (i.e., Cumulative Illness Rating Scale [CIRS], Edmonton Frail Scale [EFS], Barthel index, Short Blessed test, length of stay [LOS]) data. A multivariable analysis for assessing factors affecting resilience was fitted.ResultsOverall, 143 patients (median age 69 years, interquartile range 52–79, 74 females) were included. Resilience was significantly lower in frail (p = 0.010), elderly (p = 0.021), dependent (p = 0.032), and more clinically (p = 0.028) and cognitively compromised patients (p = 0.028), and in those with a low educational status (p = 0.032). No relation between resilience and LOS was noticed (p = 0.597). Frail patients were significantly older (p < 0.001), had a greater disease burden as measured by CIRS comorbidity (p < 0.001) and severity indexes (p < 0.001), were more dependent (p < 0.001), more cognitively impaired (p < 0.001), and displayed a lower educational level (p = 0.011) compared to non-frail patients. At multivariable analysis, frailty (p = 0.022) and dependency (p = 0.031; according to the Barthel index) were associated with lower resilience in the age groups 18–64 and ≥ 65 years, respectively.ConclusionsLow resilience was associated with frailty and dependency with an age-dependent fashion. Studies assessing the impact of this finding on important health outcomes are needed.Trial registrationClinical Complexity in Internal Medicine Wards. San MAtteo Complexity Study (SMAC); NCT03439410. Registered 01/11/2017.

Multimorbidity and quality of primary care after release from prison: a prospective data-linkage cohort study

BackgroundThe period after release from prison can be challenging, especially due to a higher risk of morbidity and mortality despite commonly increased use of healthcare services. However, little is known about the quality of the healthcare offered to this population, which limits the possibility of addressing this important health inequity. This study characterised multimorbidity and investigated the relationship between multimorbidity and quality of primary healthcare in adults within 2 years after release from prison.MethodsThis was a prospective cohort study of 1046 participants of a service brokerage intervention after release from prison between August 2008 and July 2010 in Queensland, Australia. Participants had their baseline survey and clinical data linked prospectively with their medical, correctional and death records. Multimorbidity was ascertained using the Cumulative Illness Rating Scale and classified into three categories: none, moderate (morbidity in 2–3 domains) and complex (morbidity in 4 or more domains). Outcomes were Usual Provider Continuity Index (UPCI), Continuity of Care (COC) Index, and having at least one extended primary care consultation (> 20 minutes). Descriptive statistics and logistic regression were used in the analyses.ResultsMultimorbidity was present for 761 (73%) participants, being more prevalent among females (85%) than males (69%), p < 0.001. Moderate multimorbidity was not associated with UPCI or COC, but was associated with having at least one long consultation (AOR = 1.64; 95% CI:1.14–2.39), after adjusting for covariates. Complex multimorbidity was positively associated with all outcomes in the adjusted models. Indigenous status was negatively associated with UPCI (AOR = 0.54; 95% CI: 0.37–0.80) and COC (AOR = 0.53; 95% CI: 0.36–0.77), and people younger than 25 years were at 36% lower odds (AOR = 0.64; 95% CI: 0.44–0.93) of having a long consultation than the middle-aged group (25–44 years) in the adjusted models.ConclusionModerate multimorbidity was associated with having at least one extended primary care consultation, but not with adequate continuity of care, for adults within 2 years of being released from prison. Nearly half of those with complex multimorbidity did not receive adequate continuity of care. The quality of primary care is inadequate for a large proportion of adults released from prison, constituting an important and actionable health inequity.

With great power comes great responsibility: Managing side effects of novel treatments in chronic lymphocytic leukemia (CLL)

The treatment paradigm shift in CLL has uprooted many clinicians’ standard practices. Previously, treatment largely depended on age, organ function and “fitness” based on clinical trials which used CIRS (cumulative illness rating scale) scores. Today, as a hematologist who mainly treats patients with CLL, treatment strategies are more complex and multi-factorial. Treatments are based on molecular profiling, which aids in the identification of lower-risk patients for time-limited treatment options versus higher-risk patients (IGVH unmutated, del 17p or TP534 ) who benefit from continuous therapies. The highest-risk patients can be identified using a staging system for CLL known as the CLL-International Prognostic Index (CLL-IPI). However, increased CIRS scores are prognostic for poor outcomes independent of the CLL-IPI. As a result, selecting the right treatment for the right individual has never been more important, especially in the era of novel therapeutics. This treatment selection decision pathway includes understanding both patient factors and medical factors that may influence patient outcomes.

Fever Correlation with Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Concentrations in Patients with Isolated Polymyalgia Rheumatica (PMR): A Retrospective Comparison Study between Hospital and Out-of-Hospital Local Registries.

Background: Polymyalgia rheumatica (PMR) is the most common systemic inflammatory rheumatic disease affecting the elderly. Giant cell arteritis (GCA) is a granulomatous vasculitis affecting the aorta and its branches associated with PMR in up to 20% of cases. In recent studies based on university hospital registries, fever correlated with the erythrocyte sedimentation rate (ESR) but not with C-reactive protein (CRP) concentrations at the time of diagnosis in patients with isolated PMR. A long delay to a PMR diagnosis was suggested to explain this discrepancy, possibly caused by laboratory alterations (for instance, anemia of chronic disease type) that can influence only ESR. We performed a retrospective comparison study between the university hospital and two out-of-hospital public ambulatory databases, searching for any differences in fever/low-grade fever correlation with ESR and CRP. Methods: We identified all patients with newly diagnosed PMR between 2013 and 2020, only including patients who had a body temperature (BT) measurement at the time of diagnosis and a follow-up of at least two years. We considered BT as normal at <37.2 °C. Routine diagnostic tests for differential diagnostics were performed at the time of diagnosis and during follow-ups, indicating the need for more in-depth investigations if required. The GCA was excluded based on the presence of suggestive signs or symptoms and routine ultrasound examination of temporal, axillary, subclavian, and carotid arteries by experienced ultrasonographers. Patients with malignancies, chronic renal disease, bacterial infections, and body mass index (BMI) > 30 kg/m2 were excluded, as these conditions can increase CRP and/or ESR. Finally, we used the Cumulative Illness Rating Scale (CIRS) for quantifying the burden of comorbidities and excluded patients with a CIRS index > 4 as an additional interfering factor. Results: We evaluated data from 169 (73 from hospital and 96 from territorial registries) patients with newly diagnosed isolated PMR. Among these, 77.7% were female, and 61.5% of patients had normal BT at the time of diagnosis. We divided the 169 patients into two cohorts (hospital and territorial) according to the first diagnostic referral. Age at diagnosis, ESR, CRP, median hemoglobin (HB), and diagnostic delay (days from first manifestations to final diagnosis) were statistically significantly different between the two cohorts. However, when we assessed these data according to BT in the territorial cohort, we found a statistical difference only between ESR and BT (46.39 ± 19.31 vs. 57.50 ± 28.16; p = 0.026). Conclusions: ESR but not CRP correlates with fever/low-grade fever at the time of diagnosis in PMR patients with a short diagnosis delay regardless of HB levels. ESR was the only variable having a statistically significant correlation with BT in a multilevel regression analysis adjusted for cohorts (β = 0.312; p = 0.014).

P1221: DIFFUSE LARGE B-CELL LYMPHOMA RICHTER SYNDROME IN CHRONIC LYMPHOCYTIC LEUKEMIA – A RETROSPECTIVE ANALYSIS OF TREATMENT OUTCOMES IN POLISH ADULT LEUKEMIA STUDY GROUP

Background: Richter syndrome (RS) is a recognized uncommon manifestation and evolution of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with a dismal prognosis. It occurs in 2-10% of CLL patients. It is associated with a clonal evolution and progression, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or, less frequently, to Hodgkin Lymphoma (HL). Despite the advances in understanding pathogenesis of the disease, the DLBCL variant of RS (DLBCL-RS) is associated with a dismal prognosis with a median survival < 1 year. The treatment options and risk factors of worse outcome for RS still need to be further expanded. Aims: To study the characteristic and treatment outcomes of patients with DLBCL-RS. Methods: The retrospective analysis of 99 patients diagnosed with DLBCL-RS treated in hematology centers of the Polish Adult Leukemia Study Group (PALG) between 2011 and 2021. Results: Clinical data of 124 patients with Richter syndrome was collected. Ninety-nine patients were diagnosed with DLBCL-RS (79.8%) and further analyzed. Median time since CLL diagnosis to Richter transformation was 43.0 months (range 0-252.0). At the time of transformation 31.3% patients had CLL Rai stage IV, 74.7% were ECOG< 2, while the median Cumulative Illness Rating Scale (CIRS) was 4 (range 0-16). Thirty-seven patients transformed during CLL treatment, 56.7% of them were receiving novel agents (Brutons tyrosine kinase inhibitor or BCL2 inhibitor). Median time of observation after transformation was 10.7 months (range 0-98.6). Median overall survival (OS) after DLBCL-RS diagnosis was 17.3 months (95% Cl 11.9-46.8) and median progression-free survival (PFS) 13.5 months (95% Cl 9.6-22.7). Seventy-six patients (76.8%) had RS treated with intensive chemotherapy protocols, mainly R-CHOP-like regimens for the first line treatment. Only 42.3% had response to the treatment (25/76 complete responses and 11/76 partial responses). Worth mentioning is that in the group of patients with response two patients had ibrutinib monotherapy and one had rituximab-ibrutinib. In forty patients RS was primarily resistant to administered treatment and 65% of them died due to progression or treatment related complications. In the primary resistant DLBCL-RS p53 pathway aberration was noted in 47.5% of patients (17p deletion in 13 patients or TP53 mutation in 6 patients). Better results were achieved for patients who proceeded to autologous hematopoietic stem cell transplantation (auto-HSCT; n=8) and allogeneic HSCT (allo-HSCT; n=10). The median OS in auto-HSCT recipients was 46.1 months, while in allo-HSCT the median OS reached 18.3 months (3 patients died due to allo-HCST-related complications). Significantly lower OS (3.4 months, 95% Cl 14.13-not reached) was observed for RS in heavily pretreated CLL patients (>3 lines of therapy preceding transformation) compared to those treated with up to 3 lines of therapy (23.7 months) (p=0.0002). Median OS for treatment naïve patients at DLBCL-RS diagnosis was not reached. Other factors identified as predictors of poor OS in univariate analysis were ECOG ≥2 (p=0.0014), hemoglobin level <10 g/dl (p=0.017) and platelet count <100x109/L (p=0.0065). Summary/Conclusion: Our study represents the largest dataset of DLBCL-RS patients in Polish hematology centers and confirms the poor outcomes and prognosis associated with RS. The worst treatment results were observed in RS receiving >3 lines of CLL therapy preceding transformation. Only proceeding to hematopoietic stem cell transplantation may improve the prognosis.

P677: CLINICAL EFFICACY AND TOLERABILITY OF VENETOCLAX PLUS RITUXIMAB IN RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA – REAL WORLD ANALYSIS OF POLISH ADULT LEUKEMIA STUDY GROUP

Background: The introduction of venetoclax into clinical practice has improved the outcome of patients with relapsed/refractory chronic lymphocytic leukemia (RR-CLL). The results of the MURANO trial published in March 2018 showed significantly longer progression-free survival (PFS) and overall survival (OS) in RR-CLL patients treated with venetoclax and rituximab (VEN-R) comparing to bendamustine and rituximab (BR) and resulted in the approval of VEN-R in the therapy of RR-CLL in the European Union and the United States. It should be noted that the results of registration studies often do not correspond with the data from real-life observations. Aims: To study the clinical efficacy and safety profile of VEN-R treatment in RR-CLL patients outside clinical trials. Methods: We performed retrospective analysis of RR-CLL patients treated with VEN-R in hematology centers of the Polish Adult Leukemia Study Group (PALG) from 2019 to 2021. Results: Clinical data of 117 RR-CLL patients treated with VEN-R were collected. Median patient age upon initiation of VEN-R therapy was 67 years (range 33 – 84 years). Seventy-two patients (61.5%) were men. Median Cumulative Illness Rating Scale (CIRS) was 6 (range 2 - 16). Patients were treated with a median of 2 (range 1–9) previous lines of therapy, whereas 32 patients (27.4%) had relapsed following the first line of treatment. Overall, 25 patients (21.4%) had 17p deletion, whereas TP53 mutation was identified in 13 patients (11.1%). The median follow-up was 9.96 months (range 0.27 - 29.13). The overall response rate (ORR) was 95.2%. Seventeen patients (14.5%) achieved complete remission (CR), 83 (70.9%) partial remission (PR), while in 5 patients (4.3%) disease progression was noted. In the patients with 17p deletion (n=22) or TP53 mutation (n=11), CR and PR were observed in 4 (12.1%) and 29 (87.9%) patients, respectively. The median PFS in the whole cohort was 20.8 (95% CI 18.43 - not reached) months and the median OS was not reached. In our study none of the analyzed clinico-pathological factors had significant impact on ORR, PFS and OS. During the follow-up time four (3.4%) cases of Richter transformation were diagnosed. There were 18 deaths recorded during the course of observation; 3 (16.7%) due to disease progression and 7 (38.9%) due to COVID-19 infection. The others were due to infections other than SARS-CoV-2 (n=3, 16.7%) and the cause of death could not be specified in five cases (27.8%). Eighty-three patients (70.9%) remain on treatment, while treatment was discontinued in thirty-four cases (29.1%). Reasons for therapy discontinuation included patient’s death (52.9%), treatment-related cytopenias (17.6%), disease progression (14.7%), Richter’s transformation (11.8%), autoimmune hemolytic anemia (5.9%), diarrhea (2.9%) and infections (8.8%). In one case treatment discontinuation was due to consent withdrawal and one patient was lost to follow-up. The following adverse events of VEN-R treatment were reported during the study: all grade neutropenia (71.8% with grade 3/4 in 55.6%), anemia (51.3%), thrombocytopenia (47%), pneumonia (9.4%), neutropenic fever (6.8%), autoimmune hemolytic anemia (4.3%), immune thrombocytopenic purpura (1.7%), diarrhea (4.3%) and in one case exacerbation of heart failure was observed. Summary/Conclusion: In this retrospective analysis the outcomes of treatment with the VEN-R regimen in real-life setting were worse than those reported in the MURANO trial.

PB2146: A PHASE 2, OPEN-LABEL STUDY OF LONCASTUXIMAB TESIRINE IN COMBINATION WITH RITUXIMAB (LONCA-R) IN PREVIOUSLY UNTREATED UNFIT/FRAIL PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) (LOTIS-9)

Background: Rituximab in combination with chemotherapy (R [rituximab]-CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) is the standard first-line therapy for patients (pts) with DLBCL. With an aging population, unfit or frail pts who may not tolerate R-CHOP represent an increasing unmet need. There is also significant heterogeneity in how fitness for therapy is assessed. The simplified geriatric assessment (sGA) identifies three distinct categories (fit, unfit, and frail) based on age, activities of daily living (ADL), instrumental activities of daily living (IADL), and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G; Merli et al. J Clin Oncol 2021). Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin, is approved in relapsed or refractory (R/R) DLBCL based on data from the phase 2 LOTIS-2 pivotal trial (Caimi et al. Lancet Oncol 2021). The safety and efficacy of Lonca-R in combination is also being studied in pts with R/R DLBCL versus immunochemotherapy in an ongoing, separate study (LOTIS-5; NCT04384484). Aims: To determine the safety and efficacy of Lonca-R in previously untreated unfit/frail pts, as characterized by the sGA, in the LOTIS-9 clinical trial (NCT05144009). Methods: This is a phase 2, open-label, response-adapted study of Lonca-R in previously untreated unfit (Cohort A) or frail (Cohort B) pts with DLBCL. Key inclusion criteria include diagnosis of DLBCL (including DLBCL transformed from indolent lymphoma), high-grade B cell lymphoma, or grade 3b follicular lymphoma; Eastern Cooperative Oncology Group performance status of 0-2; and measurable disease (2014 Lugano Classification). Each cohort will enroll 40 pts, with fitness (Cohort A) and frailty (Cohort B) assessed using the sGA. Primary objectives are to assess efficacy (Cohorts A and B) and tolerability (Cohort B) of Lonca-R. The primary endpoint will be the complete response (CR) rate (Cohorts A and B) and tolerability defined by the percentage of patients completing a total of 4 cycles of therapy (Cohort B). Lonca-R treatment consists of R intravenously [IV] 375 mg/m2 on day 1 of cycles 1-4 (subcutaneously allowed starting at C2), Lonca 150 µg/kg IV on day 2 of cycle 1 and day 1 of cycle 2, and Lonca 75 µg/kg IV on day 1 of cycles 3 and 4. After completion of three Lonca-R cycles, pts who achieve CR or partial response (PR) will continue to receive 1 or 3 additional cycles of Lonca-R, respectively. Pts in Cohort A who do not achieve a CR or PR will discontinue treatment on study. Pts in Cohort B who achieve stable disease and derive clinical benefit, per the treating physician, may continue to receive an additional 3 cycles of Lonca-R. All pts will be followed every 12 weeks for 1 year, then every 24 weeks for up to 3 years, and then annually up to 5 years. Results: The study will open for recruitment in 2022. Summary/Conclusion: N/A

Geriatric assessment (GA) and the influence on the variability of treatment recommendations for elderly patients (pts) with gastrointestinal (GI) tumors.

12049 Background: GA is recommended to guide therapy for elderly cancer pts. To assess whether GA results influence the recommended treatment and the inter-oncologist variability of treatment recommendations, we conducted a case-vignette-based study in medical oncologists (MOs). Methods: MOs were asked to give medical treatment recommendations for GI cancer pts in three steps: (1) based on tumor findings alone to simulate the guideline recommendation for a “50-year-old standard patient (pat.) without comorbidities”, (2) for the same tumor situation in an elderly pat. according to the medical history, comorbidities, lab values and a short video simulating the clinical consultation situation and (3) after in addition the results of a full GA were disclosed (Barthel index, Cumulative Illness Rating Scale, G8, Geriatric Depression Scale, Mini Mental Status Examination, Mini-Nutritional-Assessment [MNA], Time Get Up and Go, EORTC-QLQ30 and stair climb test - each with short interpretation aid). Each MO voted for 2-4 randomly allocated pts out of a pool of 10 pts with mean age 78.5 years. A slider (like a visual analogue scale) was used to express the grade of recommendation for several treatment options per patient. The means and variances for each treatment option were calculated and compared for analysis. Results: Seventy German MOs had given 164 treatment recommendations that were substantially different for elderly compared to younger pts. The recommendations had a significantly higher variance for elderly pts than for the “standard” pts (p &lt; 0.0001) indicating a lower inter-oncologist agreement regarding the treatment recommendations in elderly pts. MOs with &gt; 6 years working experience as specialist had no lower variance in their recommendations. There was a non-significant trend towards a lower variance if the MOs were based at outpatient units of hospitals (compared to MOs working with in-patients or as private oncologists) and for MOs working at larger hospitals (&gt; 800 beds) compared to those based at smaller ones. The knowledge on the full GA results had marginal influence on the treatment recommendations itself or its variance, only (p = 0.92). In the survey, the geriatric tools were rated more than two times higher as being meaningful (53%) and useful (49%) than they were used in clinical practice (19%). The most used tool in the routine care for geriatric pts was the MNA (30%). Conclusions: There is a large variability regarding the "optimal" treatment in geriatric pts without meaningful improvement with larger working experience. Although the recommended therapeutic regime varied in elderly pts and the MOs rated the GA results as “useful”, the GA results did not influence the individual recommendations or its variance, and GA is rarely used in daily practice indicating that more research on an effective implementation into the clinical practice is needed.

Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities

BackgroundGLOW is a phase 3 trial evaluating the efficacy and safety of ibrutinib-venetoclax in older patients and/or those with comorbidities with previously untreated chronic lymphocytic leukemia (CLL).MethodsWe randomly assigned (1:1) patients 65 years of age or older or those 18 to 64 years of age who also had a Cumulative Illness Rating Scale (CIRS) score greater than 6 (CIRS scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or creatinine clearance of less than 70 ml/min, to ibrutinib-venetoclax (3 cycles ibrutinib lead-in, then 12 cycles ibrutinib-venetoclax) or chlorambucil-obinutuzumab (6 cycles). The primary end point was progression-free survival (PFS) assessed by an independent review committee. Secondary end points included undetectable minimal residual disease (uMRD), response rates, and safety.ResultsThis study enrolled 211 patients, with 106 randomly assigned to ibrutinib-venetoclax and 105 to chlorambucil-obinutuzumab. With a median follow-up of 27.7 months, there were 22 PFS events for ibrutinib-venetoclax and 67 events for chlorambucil-obinutuzumab. PFS was significantly longer for ibrutinib-venetoclax than for chlorambucil-obinutuzumab (hazard ratio, 0.216; 95% confidence interval [CI], 0.131 to 0.357; P<0.001). The improvement in PFS with ibrutinib-venetoclax was consistent across predefined subgroups, including patients 65 years of age or older or with a CIRS score greater than 6. The best uMRD rate in bone marrow by next-generation sequencing was significantly higher for ibrutinib-venetoclax (55.7%) than for chlorambucil-obinutuzumab (21.0%; P<0.001). The proportion of patients with sustained uMRD in peripheral blood from 3 to 12 months after end of treatment was 84.5% for ibrutinib-venetoclax and 29.3% for chlorambucil-obinutuzumab. Four patients treated with ibrutinib-venetoclax required subsequent therapy compared with 27 patients receiving chlorambucil-obinutuzumab (hazard ratio, 0.143; 95% CI, 0.050 to 0.410). Adverse events grade 3 or greater occurred for 80 (75.5%) and 73 (69.5%) patients receiving ibrutinib-venetoclax and chlorambucil-obinutuzumab, respectively, with neutropenia being most common in both arms (37 [34.9%] and 52 [49.5%]). There were 11 (10.4%) and 12 (11.4%) all-cause deaths in the ibrutinib-venetoclax and chlorambucil-obinutuzumab arms, respectively.ConclusionsIbrutinib-venetoclax, an all-oral, once-daily, fixed-duration combination, demonstrated superior PFS and deeper and better sustained responses versus chlorambucil-obinutuzumab as first-line CLL treatment in older patients and/or those with comorbidities. (Funded by Janssen Research & Development, LLC, and Pharmacyclics; ClinicalTrials.gov number, NCT03462719.)

The Prognostic Value of Eight Comorbidity Indices in Older Patients with Cancer: The ELCAPA Cohort Study.

Simple SummaryA prognostic assessment is crucial for making cancer treatment decisions. However, the frequent presence of comorbidities makes this assessment particularly challenging in older adults. Many comorbidity indices are available, but none have been developed for older patients with cancer. We assessed the prognostic performance (relative to one-year mortality) of eight comorbidity indices in a cohort of older patients with cancer. All the comorbidity indices were independently associated with 1-year mortality in the whole study population, and had very good discriminant ability. Among patients with metastatic cancer, only CIRS-G was independently associated with 1-year mortality.Background: A prognostic assessment is crucial for making cancer treatment decisions in older patients. We assessed the prognostic performance (relative to one-year mortality) of eight comorbidity indices in a cohort of older patients with cancer. Methods: We studied patients with cancer aged ≥70 included in the Elderly Cancer Patient (ELCAPA) cohort between 2007 and 2010. We assessed seven nonspecific indices (Charlson Comorbidity Index (CCI), three modified versions of the CCI, the Elixhauser Comorbidity Index, the Gagne index, and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G)) and the National Cancer Institute Comorbidity Index. Results: Overall, 510 patients were included. Among patients with nonmetastatic cancer, all the comorbidity indices were independently associated with 1-year mortality (adjusted hazard ratios (aHRs) of 1.44 to 2.51 for one standard deviation increment; p < 0.05 for all) and had very good discriminant ability (Harrell’s C > 0.8 for the eight indices), but were poorly calibrated. Among patients with metastatic cancer, only the CIRS-G was independently associated with 1-year mortality (aHR (95% confidence interval): 1.26 [1.06–1.50]). Discriminant ability was moderate (0.61 to 0.70) for the subsets of patients with metastatic cancer and colorectal cancer. Conclusion: Comorbidity indices had strong prognostic value and discriminative ability for one-year mortality in older patients with nonmetastatic cancer, although calibration was poor. In older patients with metastatic cancer, only the CIRS-G was predictive of one-year mortality.

A comparison of two approaches for modeling dementia progression in a changing patient context.

ObjectivesTo explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time‐varying comorbidity and frailty.MethodsWe used individual growth models to study baseline and time‐varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini‐Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS‐G).ResultsAlthough baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time‐varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9‐point lower MMSE score (p = 0.03) and a 14.9‐point lower DAD score (p < 0.01). A 1‐point increase in CIRS‐G score was associated with a 1.1‐point lower DAD score (p < 0.01).ConclusionsTime‐varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context.

Cardiovascular disease patients and predictors of length of stay of residential of cardiac rehabilitation. A specific rehabilitation is mandatory in very old patients?

As more adults are living into old age, they are predisposed to cardiovascular disease (CVD) and the demand for cardiac rehabilitation is increasing. We aimed to verify predictors of length of stay (LOS) in young (Y) vs older (O) vs very old (VO) CVD patients, admitted to residential cardiac rehabilitation. Patients' demographic and clinical characteristics at admission, as well as Barthel index (BI), Cumulative Illness Rating Scale (CIRS), comorbidity severity/complexity, NYHA classification, left ventricular ejection fraction (LVEF), physical activity level were compared in Y (≤65 years) vs O (between >65 and <76 years) vs VO patients (with an age of ≥76 years) against LOS. In 5,070 consecutively CVD patients were included; they were 1392 Y (38%) 1944 O (35%) 1334 VO patients (27%) and LOS duration was 16±7, 19±9 and 22±10 days, respectively (p<0.0001). In Y, LOS was linked to BI (p=0.000) and to LVEF (p=0.000) at multivariable analysis with area under ROC curve of 0.82, whereas in O, LOS was associated to gender (p=0.013) CIRS severity (p=0.000), BI (p=0.000), LVEF (p=0.000), and in those VO to gender (p=0.004), BI (p=0.000) and medical infusion (p=0.000) at multivariable with ROC curve of 0.83 and 0.74, respectively. In very old patients, a prolonged LOS is related to extra-cardiac conditions. Therefore, we promote a specific cardiac rehabilitation for these patients.

Depression in internal medicine inpatients at the time of hospital discharge and referral to primary care

Background and objectivesThis is the first multi-center study intended to document the prevalence, characteristics, and associations of depression in Medicine patients at the time of hospital discharge and their referral to Primary Care (PC). MethodsAdult patients randomly selected among consecutive admissions to Medicine wards in 8 hospitals in Spain, covering health districts, were examined in a two-phase 'case-finding' procedure. Standardized, Spanish versions of instruments were used, including the Standardized Polyvalent Psychiatric Interview (SPPI) and Cumulative Illness Rating Scale (CIRS). Cases of depression were diagnosed according to ICD-10 general hospital research criteria. ResultsThree hundred and twelve patients with treatable depression and 777 non-depressed controls were identified. In a conservative estimate, the global prevalence of major depression was 7.1%, dysthymia 4.2% and adjustment depression 7.1%, and 51.9% of cases were of moderate/ severe intensity. Depression was more frequent in women, the differences being significant in all categories of depression. The prevalence of depression was lower in individuals aged 85 or more years, the differences being significant in cases of both dysthymia and adjustment depression. A clear pattern of decreasing prevalence with age was observed in women. The depressed had as an average five medical systems affected, and higher CIRS scores compared with the controls, the differences being significant in cases of both major depression and dysthymia. ConclusionsThis is the first report showing a considerable prevalence of treatable cases of depression in Medicine patients at the time of hospital discharge and referral to PC. Depression is associated with the severity of the medical condition, and differences observed by age and sex have clinical implications. Paper read at the 3rd Annual Meeting of the European Association of Psychosomatic Medicine, Nuremberg 2015.

Guideline for the treatment of chronic lymphocytic leukaemia

Guideline for the treatment of chronic lymphocytic leukaemia

The effect of cognitive function and central nervous system depressant use on mortality-A prospective observational study of previously hospitalised older patients.

Older patients are often users of prolonged Central Nervous System Depressants (CNSD) (Z-hypnotics, benzodiazepines and opioids), which may be associated with reduced cognition. The long-term effects of CNSD use and reduced cognitive function in older patients are unclear. The aim of this study was to examine whether cognitive function and CNSD use at baseline hospitalisation were associated with all-cause mortality two years after discharge. We conducted a prospective observational study, including baseline data (2017-2018) from previously hospitalised older patients (65-90 years), assessing all-cause mortality two years after discharge. We used logistic regression to assess the primary outcome, all-cause mortality two years after baseline hospitalisation. The primary predictors were cognitive function measured by The Mini Mental State Examination (MMSE) and prolonged CNSD use (continuous use ≥ 4 weeks). Adjustment variables: age, gender, education, the Hospital Anxiety and Depression Scale (HADS) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), using receiver operating characteristics (ROC) to compare the predictive power of the models. In a sub-analysis we used, the Neurobehavioural Cognitive State Examination (Cognistat) and the Clock Drawing Test. Two years after discharge, out of 246 baseline patients, 43 were deceased at follow-up, among these 27 (63%) were CNSD users, and 16 (36%) were non-users at baseline, (p = 0.002). In the multivariable models cognitive function (MMSE score) was a predictor of mortality (OR 0.81 (95% CI 0.69; 0.96), p = 0.014). CNSD use was associated with mortality (OR 2.71 (95% CI 1.06; 6.95), p = 0.038), with ROC AUC: 0.74-0.77 for these models. Results using Cognistat supported the findings. The Clock Drawing Test was not significant predictor of mortality. Two years after discharge from the hospital, older patients with reduced cognitive function and CNSD use during hospital stay had higher mortality. This underlines that inappropriate (prolonged and concurrent) use of CNSDs should be avoided by older patients, particularly in patients with reduced cognitive function. NCT03162081, 22 May 2017.

Contribution of clinical severity and geriatric risk factors in predicting short-term mortality of older hospitalized pneumonia patients: the Pneumonia in Italian Acute Care for Elderly units (PIACE) study.

Clinical severity of pneumonia in older persons increases the risk for short-term mortality. Comprehensive geriatric assessment (CGA) may provide further insight in prognostic stratification. To investigate whether CGA may improve prognostic stratification among older patients with pneumonia admitted to hospital. Our series consisted of 318 consecutive patients hospitalized for pneumonia in a multicenter observational study. Disease severity was assessed by Sequential Organ Failure Assessment (SOFA) and Pneumonia Severity Index (PSI). CGA included the occurrence of delirium, Basic Activities of Daily Living (BADL) disability, cognitive impairment at Short Portable Mental Status Questionnaire (SPMSQ) and overall comorbidity assessed by Cumulative Illness Rating Scale (CIRS). The outcomes were in-hospital and post-discharge 3month mortality. Statistical analysis was carried out by Cox regression, area under receiver operating curve (AUC) and net reclassification index (NRI). Overall, 53 patients died during hospitalization and 52 after discharge. Delirium, SOFA score and admission BADL disability were significant predictors of in-hospital mortality. SOFA score, CIRS, previous long-term oxygen therapy and discharge BADL dependency significantly predicted post-discharge mortality. The accuracy of SOFA in predicting in-hospital and post-discharge mortality was fair (AUC = 0.685, 95% CI = 0.610-0.761 and AUC = 0.663, 95% CI = 0.593-0.734, respectively). BADL dependency and delirium improved predictive accuracy for in-hospital mortality (ΔAUC = 0.144, 95% CI = 0.062-0.227, p < 0.001), while pre-admission oxygen therapy, CIRS and BADL dependency improved predictivity for 3month mortality (ΔAUC = 0.177, 95% CI = 0.102-0.252, p < 0.001). Among older pneumonia patients, prognostic stratification obtained by clinical severity indexes is significantly improved by CGA risk factors. CGA provides important information for prognostic stratification and clinical management of older pneumonia patients.

Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia

BackgroundChronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB).MethodsA retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan–Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy.ResultsForty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil.ConclusionsIn summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.