Patients In Daily Clinical Practice Research Articles

La radiothérapie des CBNPC de stade III : nouvelles techniques, nouvelles combinaisons

Defining the optimal treatment approach for patients with stage III non-small cell lung cancer, where the loco-regional disease extension renders a surgical approach obsolete, represents an important clinical challenge. In addition, many of these patients present with several comorbidities, compromising their tolerance to treatment. This article describes how innovative radiotherapy approaches try to enhance loco-regional tumour control as a first step towards improved survival, often by exploring novel avenues to dose-escalation, while at the same time focus on limiting early and long-term radiation-induced toxicity by applying the most advanced radiotherapy techniques. Moreover, the path towards new combinations with systemic agents, particularly immunotherapy building on the actual standard of combined chemo-radiotherapy with durvalumab in consolidation, is reported. This article wants to give a balanced view on the importance to investigate how we can obtain better local and metastatic disease control by intensifying our combined treatment strategies, while bearing in mind that many of our patients in daily clinical practice may not be able tolerate this. This urges us to also explore less disruptive treatment approaches for our more frail and aged patient population and define in a multidisciplinary manner the most optimal treatment strategy for each individual patient in our daily clinical practice.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small-cell lung cancer (NEJ056).

Locoregional recurrence of non-small-cell lung cancer (NSCLC) after complete resection lacks standard treatment. Durvalumab after chemoradiotherapy (CRT) or CRT alone is often selected in daily clinical practice for patients with locoregional recurrence; however, the therapeutic efficacy of these treatments remains unclear, and we aimed to assess this. This retrospective observational study used data from patients with NSCLC diagnosed with locoregional recurrence after complete resection who subsequently underwent concurrent CRT followed by durvalumab (CRT-D group) or CRT alone (CRT group). We employed propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for various confounders and evaluate efficacy in the CRT-D group. After IPTW adjustment, the CRT-D group contained 119 patients (64.7% male; 69.7% adenocarcinoma), and the CRT group contained 111 patients (60.5% male; 73.4% adenocarcinoma). Their mean ages were 66 and 65 years, respectively. The IPTW-adjusted median progression-free survival was 25.4 and 11.5 months for the CRT-D and CRT groups, respectively (hazard ratio, 0.44; 95% confidence interval, 0.30-0.64); the median overall survival was not reached in either group favoring CRT-D (hazard ratio, 0.49; 95% confidence interval, 0.24-0.99). Grade 3 or 4 adverse events were observed in 48.8% of patients during CRT, 10.7% after initiating durvalumab maintenance therapy in the CRT-D group, and 57.3% in the CRT group. Overall, the sequential approach of CRT followed by durvalumab is a promising treatment strategy for locoregional recurrence of NSCLC after complete resection.

Understanding how a personalized risk prediction tool (VALUE-PERSARC) supports informed treatment decisions of soft-tissue sarcomas patients in daily clinical practice – A mixed methods study

IntroductionRisk prediction models (RPM) can help soft-tissue sarcoma(STS) patients and clinicians make informed treatment decisions by providing them with estimates of (disease-free) survival for different treatment options. However, it is unknown how RPMs are used in the clinical encounter to support decision-making. This study aimed to understand how a PERsonalised SARcoma Care (PERSARC) RPM is used to support treatment decisions and which barriers and facilitators influence its use in daily clinical practice. MethodsA convergent mixed-methods design is used to understand how PERSARC is integrated in the clinical encounter in three Dutch sarcoma centers. Data were collected using qualitative interviews with STS patients (n = 15) and clinicians (n = 8), quantitative surveys (n = 50) and audiotaped consultations (n = 30). Qualitative data were analyzed using thematic analysis and integrated with quantitative data through merging guided by the SEIPS model. ResultsPERSARC was generally used to support clinicians’ proposed treatment plan and not to help patients weigh available treatment options. Use of PERSARC in decision-making was hampered by clinician’s doubts about whether there were multiple viable treatment options,the accuracy of risk estimates, and time constraints. On the other hand, use of PERSARC facilitated clinicians to estimate and communicate the expected benefit of adjuvant therapy to patients. ConclusionPERSARC was not used to support informed treatment decision-making in STS patients. Integrating RPMs into clinical consultations requires acknowledgement of their benefits in facilitating clinicians' estimation of the expected benefit of adjuvant therapies and information provision to patients, while also considering concerns regarding RPM quality and treatment options' viability.

Efficacy of the Cardiac Implantable Electronic Device Multisensory Triage-HF Algorithm in Heart Failure Care: A Real-World Clinical Experience.

Heart failure (HF) admissions are burdensome, and the mainstay of prevention is the timely detection of impending fluid retention, creating a window for medical treatment intensification. This study evaluated the accuracy and performance of a Triage-HF-guided carepath in real-world ambulatory HF patients in daily clinical practice. In this prospective, observational study, 92 adult HF patients (71 males (78%), with a median age of 69 [IQR 59-75] years) with the Triage-HF algorithm activated in their cardiac implantable electronic devices (CIEDs), were monitored. Following high-risk alerts, an HF nurse contacted patients to identify signs and symptoms of fluid retention. The sensitivity and specificity were 83% and 97%, respectively. The positive predictive value was 89%, and negative predictive value was 94%. The unexplained alert rate was 0.05 alerts/patient year, and the false negative rate was 0.11 alerts/patient year. Ambulatory diuretics were initiated or escalated in 77% of high-risk alert episodes. In 23% (n = 6), admission was ultimately required. The median alert handling time was 2 days. Fifty-eight percent (n = 18) of high-risk alerts were classified as true positives in the first week, followed by 29% in the second-third weeks (n = 9), and 13% (n = 4) in the fourth-sixth weeks. Common sensory triggers included an elevated night ventricular rate (84%), OptiVol (71%), and reduced patient activity (71%). The CIED-based Triage-HF algorithm-driven carepath enables the timely detection of impending fluid retention in a contemporary ambulatory setting, providing an opportunity for clinical action.

Expert consensus recommendations on the daily clinical use of pembrolizumab for early triple-negative breast cancer.

e12521 Background: Triple-negative breast cancer (TNBC) accounts for 10–15% of all breast cancer cases and is associated with poor outcomes. Neoadjuvant chemotherapy is the standard treatment for early TNBC (eTNBC) to achieve a pathologic complete response which is associated with long-term clinical outcomes and to guide adjuvant treatment for residual disease after definitive surgery. Pembrolizumab, a programmed death 1 (PD-1) inhibitor, is approved for the peri-operative treatment of stage II and III TNBC. The Hong Kong Breast Cancer Foundation (HKBCF) convened a multi-disciplinary consensus consisting of surgeons, and clinical and medical oncologists to discuss the implementation of immunotherapy in the peri-operative setting and provide expert guidance on topics lacking definitive evidence from the KEYNOTE-522 study in daily clinical routine. Methods: The panel included 7 breast surgeons, 6 clinical oncologists, and 3 medical oncologists representing the academic, public, and private settings in Hong Kong. A modified Delphi panel was conducted, testing the panel on 7 different topics and 45 statements relating to the peri-operative treatment of eTNBC. Evidence was graded according to GRADE. Statements were initially voted by online form on a 6-point Likert scale, and the results were discussed during a consensus meeting. Consensus to accept was considered at a median ≥5 and an IQR ≤1.75 and consensus to reject at median ≤2 and an IQR ≤1.75. Results: Key findings are that the panel considered 1) the uncommon subtype “oestrogen receptor (ER)-low” does not formally meet the definition of TNBC but should be treated as TNBC; 2) pembrolizumab as a viable addition in the peri-operative setting; 3) guideline-recommended NAC for cT1c disease may be considered; but 4) this does not necessarily mean immunotherapy should be added, though it may be considered case-by-case. Furthermore, the panel 5) agreed that pembrolizumab prescription does not need to be guided by PD-L1 expression, and 6) that for patients with residual disease after NAC plus pembrolizumab, the addition of capecitabine to pembrolizumab is acceptable, however, 7) was divided about the addition of a PARPi to pembrolizumab for patients with a germline BRCA1/2 mutation (g BRCA1/2m) and residual disease — guided by the lack of routine g BRCA1/2m testing in Hong Kong. Finally, the panel 8) proposed to recommend adhering to the KEYNOTE-522 weekly paclitaxel regimen with a subclause to consider 3-weekly regimen as an alternative for specific technical or logistical challenges. Conclusions: The KEYNOTE-522 study has provided robust evidence on the efficacy and safety of peri-operative pembrolizumab in eTNBC patients. However, several clinical questions remain unanswered, and until further evidence is available, the HKBCF recommendations provide expert guidance on the use of pembrolizumab for eTNBC patients in daily clinical practice.

Predicting solute transfer rate in patients initiating peritoneal dialysis

BackgroundWhile assessment of membrane characteristics is fundamental to peritoneal dialysis (PD) prescription in patients initiating therapy, peritoneal equilibration test has theoretical and practical drawbacks. We wished to determine whether an equation using simple clinical variables could predict fast (above population mean) peritoneal solute transfer rate without dialysate sampling.MethodsWe measured peritoneal solute transfer rate, as determined by peritoneal equilibration test using the 4-h dialysate to plasma creatinine ratio, in consecutive PD outpatients attending a single tertiary hospital for their first clinical follow-up within 3 months of dialysis initiation. An equation estimating peritoneal solute transfer rate based on readily available clinical variables was generated in a randomly selected modeling group and tested in a distinct validation group.ResultsWe included 712 patients, with 562 in the modeling group and 150 in the validation group. Mean age was 58.4 ± 15.9 with 431 (60.5%) men. Mean peritoneal solute transfer rate value was 0.73 ± 0.13. An equation based on gender, race, serum sodium and albumin yielded a receiving operator characteristics (ROC) area under the curve (AUC) to detect fast peritoneal solute transfer rate (> 0.73) of 0.74 (0.67–0.82). Estimated peritoneal solute transfer rate values based on percentiles 15th (> 0.66), 20th (> 0.68), 25th (> 0.69) and 30th (> 0.70) could rule out fast peritoneal solute transfer rate with negative predictive values of 100%, 93.5%, 84.2% and 80.0%, respectively.ConclusionsAn equation based on simple clinical variables allows ruling out fast transport in a significant proportion of patients initiating PD with a high degree of confidence without requiring dialysate sampling. This could prove useful in guiding dialysis prescription of PD patients in daily clinical practice, particularly in low-resource settings.Graphical abstract

Video-Based Detection of Freezing of Gait in Daily Clinical Practice in Patients With Parkinsonism.

Freezing of gait (FoG) is a prevalent symptom among individuals with Parkinson's disease and related disorders. FoG detection from videos has been developed recently; however, the process requires using videos filmed within a controlled environment. We attempted to establish an automatic FoG detection method from videos taken in uncontrolled environments such as in daily clinical practices. Motion features of 16 patients were extracted from timed-up-and-go test in 109 video data points, through object tracking and three-dimension pose estimation. These motion features were utilized to form the FoG detection model, which combined rule-based and machine learning-based models. The rule-based model distinguished the frames in which the patient was walking from those when the patient has stopped, using the pelvic position coordinates; the machine learning-based model distinguished between FoG and stop using a combined one-dimensional convolutional neural network and long short-term memory (1dCNN-LSTM). The model achieved a high intraclass correlation coefficient of 0.75-0.94 with a manually-annotated duration of FoG and %FoG. This method is novel as it combines object tracking, 3D pose estimation, and expert-guided feature selection in the preprocessing and modeling phases, enabling FoG detection even from videos captured in uncontrolled environments.

The first experience with the use of divozilimab in the treatment of multiple sclerosis patients in daily clinical practice

The aim of this study is to assess the efficacy and safety of divozilimab in patients who have received post-marketing treatment and participants of clinical trials BCD-132-2 and BCD-132-4 were conducted at the IHB RAS. Additionally, we will present a case report of divozilimab therapy in a patient with highly active multiple sclerosis (MS). The study included 27 patients with MS. We assessed the dynamics of neurological status, magnetic resonance imaging (MRI) findings, and disability level during divozilimab treatment. We also analyzed the incidence and severity of adverse events (AE), including infusion reactions. During treatment with divozilimab, no exacerbations or radiological disease activity were observed after the first six months. Complete clinical remission was achieved in 25 patients. All 12 patients who received the drug as part of post-marketing use met the NEDA-3 criteria, and five of them showed improvement. Most AE were mild, none exceeding grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE). Laboratory parameter changes were also mild and did not exceed I-II grade according to CTCAE. There were no instances of therapy discontinuation due to intolerance. The data from post-registration use of divozilimab confirm the results of clinical trials, showing high efficacy of the drug with a predictable and favorable safety profile.

Bridging the gap in cardiovascular care in diabetic patients: are cardioprotective antihyperglycemic agents underutilized?

ABSTRACT Introduction Atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) are two major complications of type 2 diabetes (T2DM). Cardiovascular protection is a key objective, yet not fully reached in clinical practice. Areas covered Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven their efficacy in reducing major cardiovascular events in high-risk patients with T2DM and SGLT2is in reducing hospitalization for HF in placebo-controlled randomized trials. However, real-life studies worldwide revealed that only a minority of patients with T2DM receive either a GLP-1RA or an SGLT2i and surprisingly even less patients with established ASCVD or HF are treated with these cardioprotective antihyperglycemic agents. Expert opinion Bridging the gap between evidence-based cardiovascular protection with GLP-1RAs and SGLT2is and their underuse in daily clinical practice in patients with T2DM at high risk is crucial from a public health viewpoint. However, the task appears hazardous and the goal not attained considering the current failure. Education of specialists/primary care physicians and patients is critical. Multifaceted and coordinated interventions involving all actors (physicians, patients and broadly health-care system) must be implemented to stimulate the adoption of these cardioprotective antihyperglycemic medications as part of routine cardiovascular care among patients with T2DM.

Effectiveness and Safety After a Switch to Tildrakizumab: A Real World Multicenter Italian Study in Psoriasis.

Tildrakizumab is a humanized IgG1κ monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved in 2018 for the treatment of patients with moderate-to-severe chronic plaque psoriasis. This study aimed to evaluate the effectiveness, safety and survival of tildrakizumab in the medium term (48 weeks) in psoriatic patients failure to previous biologic treatment in a real world setting. This was a retrospective, multicenter observational study that included adult patients with moderate-to-severe plaque psoriasis, failure to previous biologic therapy, consecutively treated with tildrakizumab. Psoriasis Area Severity Index (PASI) and Body Surface Area (BSA) values were recorded at baseline, at 12 and 48 weeks of treatment. Safety and tolerability of tildrakizumab were investigated by examining the presence of any adverse events. Overall 51 patients were enrolled. Baseline disease severity was moderate to severe with a mean PASI score of 19.2 ± 8.5, mean BSA of 16 ± 10.4, and mean Dermatology Life Quality Index (DLQI) of 18.2 ± 6.8. A significant reduction in the mean PASI score was detected at 12 weeks of tildrakizumab therapy (3.5 ± 2.7, P < 0.001), with a further improvement at week 48 (0.6 ± 1.5, P < 0.001). At week 12, there was a great improvement in BSA score for all groups (P <0.001) with further increase at week 48. The effectiveness was confirmed also by DLQI assessment, with a significant decrease at week 12 and even more at week 48 (P <0.001). This study confirms the effectiveness of tildrakizumab in daily clinical practice in patients with moderate-to-severe plaque psoriasis.

Construct validity and responsiveness of feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis

ObjectiveThere is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue...

Retrospective Analysis of Subsolid Nodules' Frequency Using Chest Computed Tomography Detection in an Outpatient Population.

The study was designed to evaluate the frequency of detection and the characteristics of subsolid nodules (SSNs) in outpatients' chest computed tomography (CT) scans from a private hospital in Southern Brazil. A retrospective analysis of all chest CT scans was performed in adult patients from ambulatory care (non-lung cancer screening population) over a thirty-day period. Inclusion criteria were age > 18 years and lung-scanning protocols, including standard-dose high-resolution chest CT (HRCT), enhanced CT, CT angiography, and low-dose chest CT (LDCT). SSNs main features collected were mean diameter, number, density (pure or heterogenous ground glass nodules and part-solid), and localization. TheLungRADS system and the updated Fleischner Society's pulmonary nodules recommendations were used for categorization only for study purposes, although not specifically fitting the population. The presence of emphysema, as well as calcified and solid nodules were also addressed. Statistical analysis was performed using R software, categorial variables are shown as absolute or relative frequencies, and continuous variables as mean and interquartile ranges. Chest computed tomography were performed in 756 patients during the study period (September 2019), and 650 met the inclusion criteria. The IQR for age was 53/73 years; most participants were female (58.3%) and 10.6% had subsolid nodules detected. The frequency of SSNs detection in patients in daily clinical practice, not related to screening populations, is not negligible. Regardless of the final etiology, follow-up is often indicated, given the likelihood of malignancy for persistent lesions.

Treatment patterns of individualized real-life tapering approaches based on shared decision-making in rheumatoid arthritis.

To provide real-world evidence on patient-individual tapering patterns of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in daily clinical practice. Data obtained through acontrolled prospective cohort study in Germany conducted from July 2018 to March 2021 were analyzed. Participants consist of RA patients in sustained remission who were eligible for DMARD tapering at enrolment. Data from RA patients who experienced tapering of DMARDs at least once during the observational period (n = 200) were used. Descriptive analyses of medical outcomes at baseline and at time of first tapering, time to first tapering, tapering patterns by substance group, and tapering intensity were documented. We did not observe meaningful differences in either disease activity or quality of life measures between substance groups at enrolment, time of first tapering, and at 6or 12months after tapering. Median time until first tapering varied between substance groups (csDMARDs: 108days; bDMARDs: 189days; combination: 119days). Most patients received one iteration of tapering only (147/200patients, 73.5%). Dose reduction was applied for patients treated with csDMARDs (79/86patients, 91.8%), spacing of interval was the most frequent strategy for patients treated with bDMARDs only (43/48patients, 89.5%). Necessity for increased DMARD dosage was observed in only 10% of patients (20/200). Tapering intensity by substance was overall heterogenous, indicating high individualization. We identify highly heterogeneous tapering patterns between substance groups and within substances. Identification and recognition of patient-individual approaches of tapering will help to further improve the management of RA for both patients and rheumatologists.

The SOS-SAH questionnaire in clinical practice: a multi-method evaluation study

BackgroundIn patients with mild disabilities after aneurysmal subarachnoid hemorrhage (aSAH), invisible symptoms might be easily overlooked during consultations in the outpatient clinic. We hypothesize that the Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage (SOS-SAH), a disease-specific patient-reported outcome measure, might aid in screening for symptoms after aSAH. The objective of this explorative study is to evaluate the perceived impact of using the SOS-SAH in daily clinical practice for patients after aSAH, as well as to explore potential barriers to further implementation.MethodsThis multi-method study consists of a quantitative and a qualitative component. To evaluate differences in quality of care, a patient experience survey was sent to patients receiving usual care and to patients who received the SOS-SAH. A multiple linear regression model was applied, with the intervention group and case mix adjusters as independent variables. We described differences in the number of symptoms discussed between patients receiving usual care and those receiving care post-implementation. Following implementation, 16 patients and 6 healthcare professionals were interviewed about their perceptions concerning the impact of and barriers to using the SOS-SAH. A thematic analysis was performed to identify the main themes.ResultsThe survey did not reveal any differences between the usual-care group and the post-implementation group on the scales of the patient experience survey. After implementation of the SOS-SAH, the number of symptoms discussed during consultation did not increase. The interviews suggest that the SOS-SAH may improve the preparation of patients by providing them with greater insight into their complaints and by raising issues for the consultation. It could also enhance the structure and efficiency of consultation, in addition to improving communication about issues that matter to patients. All patients and healthcare professionals recommended continuing the use of the SOS-SAH in daily practice.ConclusionsAlthough no quantitative improvements were found in patient experience and symptoms discussed during consultation, implementation of the SOS-SAH could aid in screening for symptoms in patients after aSAH, and it might have a positive influence on patient preparation, while helping to structure consultations between patients and healthcare professionals.

Improvement in Quality of Life and Motor Function during Daily Clinical Practice using Directional DBS Systems (P4-11.010)

<h3>Objective:</h3> To understand the benefits of Deep Brain Stimulation (DBS) systems with Multiple Independent Current Control (MICC) in daily clinical practice in patients with Parkinson’s disease (PD). <h3>Background:</h3> The main goal of DBS therapy is to achieve optimal outcomes while avoiding side effects. The challenging anatomy surrounding DBS targets requires precise control of neurostimulation. Directional DBS systems can deliver specific amounts of current to each contact using MICC, and this capability has been shown to increase therapeutic window under controlled study conditions (Dembek 2017; Schnitzler 2022). In so doing, vertical and horizontal steering of cathodic and/or anodic current can be achieved, thereby providing flexible programming options to deliver stimulation while minimizing side effects (Steigerwald 2016) (Kirsch 2018). <h3>Design/Methods:</h3> This is a prospective, multicenter (International), registry of up to 1500-patients implanted with directional MICC-based DBS systems (Vercise, Boston Scientific), per standard-of-care. Participants are being followed up to 3-years post-implantation whereby quality-of-life, motor symptoms improvement, overall satisfaction, and other disease aspects are measured. Adverse events and device-related complications are collected. <h3>Results:</h3> A total of 815-patients have been evaluated. Quality-of-life as assessed by PDQ-39 out to 2-years demonstrated sustained clinically significant improvement (minimal clinically important difference [MCID] &gt;4.7-points) despite an expected 5-point worsening due to disease progression (p&lt;0.001) (Horvath 2017; Reuther 2007). Improvement in motor function (MDS-UPDRS III Meds-OFF ) versus baseline were also noted (35% reduction at 2-year; p&lt;0.0001). To date, with &gt;1500 directional leads implanted, no lead breakages have been reported. <h3>Conclusions:</h3> This on-going registry represents the first large-scale collection of real-world, long-term outcomes using MICC-based directional DBS systems. Use of directional DBS systems in clinical practice has been demonstrated to be beneficial per increases in therapeutic window and associated positive outcomes. Results from this on-going evaluation demonstrate sustained improvement in overall outcomes with the use of directional DBS systems. <b>Disclosure:</b> Dr. Deuschl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Cavion Functional Neuromodulation. The institution of Dr. Deuschl has received research support from Medtronic. Dr. Deuschl has received publishing royalties from a publication relating to health care. Roshini Jain has received personal compensation for serving as an employee of Boston Scientific. Roshini Jain has received stock or an ownership interest from Boston Scientific. Heleen Scholtes has received personal compensation for serving as an employee of Boston Scientific. Lilly Chen has received personal compensation for serving as an employee of Boston Scientific . Michael Barbe, MD has nothing to disclose. Steffen Paschen has nothing to disclose. Andrea Kuehn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medtronic. Andrea Kuehn has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boston Scientific. Dr. Lee has nothing to disclose. Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific . Jan Vesper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbott . Jan Vesper has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Abbott . Jan Vesper has received research support from German Research Council.

Real world experience with camrelizumab in patients with advanced non-small cell lung cancer: a prospective multicenter cohort study (NOAH-LC-101).

Camrelizumab has shown promising survival benefits in treatment-naïve advanced non-small cell lung cancer (NSCLC) patients when used in combination with chemotherapy. However, its effectiveness and safety outside the clinical trial setting are largely unknown. Therefore, we conducted NOAH-LC-101, a prospective multicenter cohort study, to investigate the real-world effectiveness and safety of camrelizumab on a large cohort of advanced NSCLC patients in daily clinical practice. All consecutive patients aged ≥18 years with confirmed advanced NSCLC scheduled for camrelizumab treatment were screened for inclusion at 43 hospitals in China. The primary outcome was progression-free survival (PFS). The secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Between August 2019 and February 2021, 403 patients were included. The median age of participants was 65 years (range, 27-87 years). There were 57 (14.1%) participants with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≥2. Most participants received camrelizumab in the second or later lines (68.7%) and plus chemotherapy (64.8%). The median PFS was 12.6 [95% confidence interval (CI): 10.7-17.0] months and median OS was 22.3 months [95% CI: 19.3-not reached (NR)]. The ORR was 28.8% (95% CI: 24.4-33.5%) and DCR was 79.9% (95% CI: 75.7-83.7%). Adverse events of any grade occurred in 348 (86.4%) participants. No new safety signals were identified. Reactive cutaneous capillary endothelial proliferation was observed in 75 (18.6%) patients, all of which were grade 1-2. This study demonstrates the effectiveness and safety of camrelizumab in a large sample of real-world NSCLC patients. The results are generally consistent with those previously reported in pivotal clinical trials. This study supports the clinical use of camrelizumab in a broader patient population (ChiCTR1900026089).

Sex differences in adverse drug reactions from Adalimumab and etanercept in patients with inflammatory rheumatic diseases

ABSTRACT Background We examine sex differences in relation to the nature, frequency, and burden of patient-reported adverse drug reactions (ADRs) in patients with inflammatory rheumatic diseases. Research design and methods Rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis patients using etanercept or adalimumab from the Dutch Biologic Monitor were sent bimonthly questionnaires concerning experienced ADRs. Sex differences in the proportion and nature of reported ADRs were assessed. Additionally, 5-point Likert-type scales reported for the burden of ADRs, were compared between sexes. Results In total 748 consecutive patients were included (59% female). From the women 55% reported ≥1 ADR, which was significantly higher than 38% of the men that reported ≥1 ADR (p < 0.001). A total of 882 ADRs were reported comprising 264 distinct ADRs. The nature of the reported ADRs differed significantly between both sexes (p = 0.02). Women in particular reported more injection site reactions than men. The burden of ADRs was similar between sexes. Conclusions Sex differences in the frequency and nature of ADRs, but not in ADR burden, exist during treatment with adalimumab and etanercept in patients with inflammatory rheumatic diseases. This should be taken into consideration when investigating and reporting results on ADRs and when counseling patients in daily clinical practice.

Regulatory Approval, Reimbursement, and Clinical Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Metastatic Breast Cancer in the Netherlands

This study found that CDK4/6 inhibitors rapidly reached many eligible patients with metastatic breast cancer and were adopted gradually over time in the Netherlands. Adoption of innovative medicines may be further optimized, and better transparency of the availability of new medicines during different phases of the postapproval access pathway is needed. This cohort study reviewed approval and reimbursement decisions of the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib and estimated the number of patients with metastatic breast cancer who were eligible for these medicines compared with the actual use in clinical practice. The study used nationwide claims data that were obtained from the Dutch Hospital Data. Claims and early access data for patients with hormone receptor-positive and ERBB2 (formerly HER2)-negative metastatic breast cancer who were treated with CDK4/6 inhibitors from November 1, 2016, to December 31, 2021, were included. The number of new cancer medicines that are being approved by regulatory agents is increasing exponentially. Yet little is known about the pace at which these medicines reach eligible patients in daily clinical practice during different phases of the postapproval access pathway. Description of the postapproval access pathway, monthly number of patients who were treated with CDK4/6 inhibitors in clinical practice, and estimated number of patients who were eligible for treatment. Aggregated claims data were used, and patient characteristics and outcomes data were not collected. To describe the entire postapproval access pathway of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the Netherlands, from regulatory approval to reimbursement and to investigate the adoption of these medicines in clinical practice among patients with metastatic breast cancer. Three CDK4/6 inhibitors have received European Union-wide regulatory approval for the treatment of HR-positive and ERBB2-negative metastatic breast cancer since November 2016. In the Netherlands, the number of patients who have been treated with these medicines increased to approximately 1847 (based on 1 624 665 claims over the entire study period) from approval to the end of 2021. Reimbursement for these medicines was granted between 9 and 11 months after approval. While awaiting reimbursement decisions, 492 patients received palbociclib, the first approved medicine of this class, via an expanded access program. By the end of the study period, 1616 patients (87%) were treated with palbociclib, whereas 157 patients (7%) received ribociclib, and 74 patients (4%) received abemaciclib. The CKD4/6 inhibitor was combined with an aromatase inhibitor in 708 patients (38%) and with fulvestrant in 1139 patients (62%). The pattern of use over time appeared to be somewhat lower compared with the estimated number of eligible patients (1847 vs 1915 in December 2021), especially in the first 2.5 years after approval.

The use of the Mini-Cog, MMSE, and GPCOG tests in domestic clinical practice for the evaluation of cognitive disorders in elderly and senile patients: the results of a survey of experts' opinions

To explore the experts' opinion on the feasibility of using Mini-Kog, MMSE and GPCOG tests for screening assessment of cognitive impairment in elderly and senile patients at the primary stage of medical care, as well as to compare different characteristics of these tests according to experts' opinion. The survey of specialists was carried out on the basis of 6 Medical Centers. Prior to the survey, specialists tested cognitive functions in elderly and senile patients during routine visits undergoing routine admission using Mini-Kog, MMSE and GPCOG tests, as well as interviewed their relatives using the corresponding section of the GPCOG. During the survey, specialists filled out a special physician checklist containing items for indicating socio-demographic information and questions regarding the use of tests for assessing cognitive functions in elderly and senile patients in daily clinical practice. The survey involved 40 specialists from different cities of Russia (mean age±SD - 38.6±14.3 years, 82.5% - women). Elderly and senile patients accounted for the predominant proportion (76-100%) of all followed-up patients. All physicians considered it important to conduct a cognitive assessment in elderly patients and they have to use various cognitive tests in their practice. According to most experts, among the Mini-Kog, MMSE and GPCOG tests, all three tools are informative, convenient and suitable for screening cognitive impairment in geriatric patients. The MMSE test is more informative and convenient. Mini-Kog, compared to the other two tools, is the simplest and most time-efficient tool that is also better perceived by patients. An advantage of the GPCOG is the possibility of participation of informants in the assessment of cognitive functions in older patients. The findings could be used in further research focused on improving the approaches for early detection of cognitive impairment in geriatric patients by primary care physicians.

ME-2: MR BLOCKERS AS THE POSSIBLE FIRST-LINE THERAPY IN HYPERTENSION

Among 43 million hypertensive patients in Japan, blood pressure levels are controlled below 140/90mmHg in only a quarter of these patients. This fact may be due to poor adherence and inadequate lifestyles as well as “clinical inertia” (“diagnostic inertia” and “treatment inertia”) of health care providers. Primary aldosteronism (PA) is the most common endocrine hypertension and often associated with resistant hypertension. Five to 10% of all people in hypertension and 20% of resistant hypertension is PA. Most importantly, PA presents with higher prevalence of cardiovascular diseases than essential hypertensive patients whose blood pressure levels are controlled to the similar levels. For the case-detection testing, high plasma aldosterone (PAC) to plasma renin activity (PRA) ratio is useful based on the clinical practice guideline of many countries. However, screening of PA is rarely done between 0.7% to 4.2% of hypertensive patients in daily clinical practice. This situation is a sad state of affairs (“diagnostic inertia”), and the screening of PA should be done at least once in all hypertensive patients. For treatment of PA, administration of a mineralocorticoid receptor blocker (MRB) is recommended in patients with bilateral PA as well as ones who do not willing to undergo surgery. It is therefore crucial to administer a MRB as a first-line therapy, although it is not included in the “first-line antihypertensives”. In addition, since the PA screening test is done quantitatively, it may be insufficient to evaluate just “non-PA” when the ratio is lower than the cut-off values. It may be rather crucial to consider the pathogenesis as “borderline aldosteronism” or “mineralocorticoid receptor (MR)-associated hypertension” when the ratio is suboptimal, because a MR antagonist would be a better choice to control hypertension under such circumstances. In diabetes mellitus and chronic kidney disease, MR may be directly overactivated by varied molecular mechanisms. In addition, under the treatment with angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in patients with diabetes and chronic kidney disease, PAC is suppressed firstly, but re-elevated sometimes over baseline levels (“aldosterone breakthrough”). We therefore presume that combination treatment of a MRB with first-line antihypertensives (ARB/ACEi and calcium channel blocker) may resolve “treatment inertia” of hypertension. Considering the resolution of both “diagnostic and treatment inertia” for hypertension, it is conceivable that MRB should be included in the first-line therapy for hypertension.