Comparative assessment of early mortality risk upon immune checkpoint inhibitors alone or in combination with other agents across solid malignancies: a systematic review and meta-analysis.

BACKGROUND: The early crossing of survival curves in randomised clinical trials (RCTs) with immune checkpoint blockers suggests an excess of mortality in the first months of treatment. However, the exact estimation of the early death (ED) rate, the comparison between ED upon immune checkpoint inhibitors (ICI) alone or in combination with other agents and the impact of tumour type, and PD-L1 expression on ED are unknown. METHODS: RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) versus non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, and the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk ratio (RR) were pooled by random effect model. RESULTS: A total of 56 RCTs (40,215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05-1.57) versus non-ICI therapies, while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73-0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26-1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED. CONCLUSIONS: ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression but preventable through the addition of other treatments to ICI.

Comparison between Ecological Momentary Assessment and Questionnaire for Assessing the Frequency of Waking-Time Non-Functional Oral Behaviours.

Over the years, several tools have been proposed to measure oral behaviours (OB). Recently, a smartphone-based application for ecological momentary assessment (EMA) has been introduced to collect real-time data on waking-time OB. The aim of this study was to compare the self-reported frequency of OB by means of a standardised questionnaire with that recorded with a smartphone-based application for EMA. A total of 151 participants, recruited from the general population, were invited to fill in the Oral Behaviour Checklist (OBC). Scores for four questions concerning grinding, clenching, tooth contact, and mandible bracing were computed. Afterwards, participants were provided with a smartphone application for prolonged real-time reporting of OB. One-way analysis of variance (ANOVA) and a general linear mixed model (GLMM) were used to compare the responses to each OBC question with the frequencies of the same condition recorded with the EMA. Results showed significant association between OBC responses and the EMA recordings. In particular, increased frequencies of clenching, grinding, and teeth contact were recorded by individuals who provided higher OBC scores. On the other hand, a nonlinear association was observed for "mandible bracing", pointing out difficulties in the comprehension of this condition.

Area Deprivation and Risk of Death and CKD Progression: Long-Term Cohort Study in Patients under Unrestricted Nephrology Care.

BACKGROUND: Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care. METHODS: We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1-4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of "goal-oriented" nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements. RESULTS: We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2-12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675). CONCLUSIONS: In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality.

[Covid-19 and clinical-epidemiological research in Italy: proposal of a research agenda on priority topics by the Italian association of epidemiology]. / Covid-19 e ricerca clinico-epidemiologica in Italia: proposta di un'agenda di ricerca su temi prioritari da parte dell'Associazione italiana di epidemiologia.

BACKGROUND: the Covid-19 pandemic has provoked a huge of clinical and epidemiological research initiatives, especially in the most involved countries. However, this very large effort was characterized by several methodological weaknesses, both in the field of discovering effective treatments (with too many small and uncontrolled trials) and in the field of identifying preventable risks and prognostic factors (with too few large, representative and well-designed cohorts or case-control studies). OBJECTIVES: in response to the fragmented and uncoordinated research production on Covid-19, the   italian Association of Epidemiology (AIE) stimulated the formation of a working group (WG) with the aims of identifying the most important gaps in knowledge and to propose a structured research agenda of clinical and epidemiological studies considered at high priority on Covid-19, including recommendations on the preferable methodology. METHODS: the WG was composed by 25 subjects, mainly epidemiologists, statisticians, and other experts in specific fields, who have voluntarily agreed to the proposal. The agreement on a list of main research questions and on the structure of the specific documents to be produced were defined through few meetings and cycles of document exchanges. RESULTS: twelve main research questions on Covid-19 were identified, covering aetiology, prognosis, interventions, follow-up and impact on general and specific populations (children, pregnant women). For each of them, a two-page form was developed, structured in: background, main topics, methods (with recommendations on preferred study design and warnings for bias prevention) and an essential bibliography. CONCLUSIONS: this research agenda represents an initial contribution to direct clinical and epidemiological research efforts on high priority topics with a focus on methodological aspects. Further development and refinements of this agenda by Public Health Authorities are encouraged.