Background Asthma prevalence increases with age, yet assessment in elderly patients is often limited by difficulties in performing reliable spirometry. Alternative, noninvasive methods such as the Forced Oscillation Technique (FOT) and fractional exhaled nitric oxide (FeNO) measurement may improve evaluation of asthma control in this population. Objective To evaluate asthma control and treatment effectiveness in elderly patients using the Asthma Control Test (ACT), GINA classification, spirometry, FOT, and FeNO, and to compare their clinical usefulness. Methods A total of 105 patients aged ≥65 years with diagnosed bronchial asthma were enrolled. All participants completed the ACT and underwent spirometry (FEV1, FVC, FEV1/FVC), FOT (R5, R20, R5–R20, X5, AX), and FeNO measurement according to ATS/ERS recommendations. Treatment intensity was classified by GINA steps (1–5). Nonparametric tests and Spearman’s rank correlation were used for statistical analysis. Results ACT scores correlated significantly with spirometric, oscillometric, and FeNO parameters. Lower ACT scores were associated with reduced FEV1% predicted and increased airway resistance and reactance (R5, AX), as well as higher FeNO levels (all p < 0.001). Patients treated at higher GINA steps (4–5) exhibited poorer asthma control, higher FeNO, and less favorable FOT indices. Reductions in FeNO following treatment intensification were accompanied by improvements in FEV1 and FOT parameters, particularly AX and R5–R20. Conclusions FOT provides a useful, noninvasive assessment of asthma control in elderly patients and complements spirometry. FeNO adds important information on airway inflammation and treatment response. Their combined use may enhance monitoring of asthma control when spirometry is limited.

Histopathological hematoxylin and eosin (H&E) slides contain valuable prognostic information for pancreatic ductal adenocarcinoma (PDAC), yet systematic feature extraction remains challenging. This multi-center study developed and validated an automated prognostic model using deep learning on digitized whole-slide images from 873 PDAC patients with surgical resection across three academic centers. The CrossFormer architecture achieved superior performance in external validation (area under the curve [AUC] = 0.774), significantly outperforming ResNet-18 (AUC = 0.716), ResNet-50 (AUC = 0.737), and DenseNet-121 (AUC = 0.729). Gradient-weighted Class Activation Mapping identified key prognostic features including desmoplastic stroma, high nuclear-to-cytoplasmic ratio, tumor necrosis, and immune cell infiltration. The pathomics signature effectively stratified patients into low-risk and high-risk groups with significant survival differences (p < 0.001). Critically, carbohydrate antigen 19-9 (CA19-9) retained prognostic value only in low-risk patients (hazard ratio [HR]= 2.70, p < 0.001) but not in high-risk patients (HR = 0.998, p = 0.990). High-risk patients derived substantial benefit from adjuvant chemotherapy (HR = 0.56, p = 0.038), whereas low-risk patients showed no significant benefit (HR = 0.83, p = 0.562). These findings provide actionable clinical insights: treatment intensification for high-risk patients and CA19-9-guided monitoring for low-risk patients. This validated, interpretable model transforms routine H&E slides into quantitative prognostic tools, enabling personalized treatment strategies without additional testing costs.

Randomized controlled trials (RCTs) have identified the additive effects of angiotensin receptor-neprilysin inhibitors (ARNIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors on neurohormonal inhibition therapy in patients with heart failure with reduced ejection fraction (HFrEF). However, their additive effects on conventional baseline therapies in patients with severe HFrEF remain unclear. A systematic review was conducted using the PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases until February 2025. Our review included RCTs that evaluated the effects of ARNIs or SGLT2 inhibitors in patients with severe HFrEF. The primary outcome was the composite endpoint of cardiovascular death or hospitalization for heart failure. The pooled hazard ratio (HR) was estimated through a network meta-analysis conducted using a frequentist statistical approach. Five relevant trials, or their New York Heart Association class III-IV subgroups, were identified, comprising a total of 4894 patients with severe HFrEF. For the addition of SGLT2 inhibitors to neurohormonal inhibitors, the HR was 0.87 (95% confidence interval 0.75-1.01). For the addition of ARNIs, the HR was 0.96 (95% confidence interval 0.83-1.12). The certainty of evidence was moderate for SGLT2 inhibitors and low for ARNIs according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Evidence for the additive effects of SGLT2 inhibitors and ARNIs in severe HFrEF remains limited, and therefore, treatment intensification with these agents should be approached with caution. International Prospective Register of Systematic Reviews (PROSPERO) identifier no. CRD42025641240.

This study aimed to determine whether there are differences in biologic treatment and complications according to subgroups of juvenile idiopathic arthritis (JIA) patients in adulthood. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) has been a single-center biologic disease-modifying anti-rheumatic drug registry since 2005. Patients were selected from HUR-BIO who met the International League of Associations for Rheumatology classification criteria for juvenile idiopathic arthritis. Enthesitis-related arthritis (82, 49.1%), rheumatoid factor (-) polyarthritis (39, 23.4%), and rheumatoid factor ( +) polyarthritis (26, 15.6%) were the most prevalent subgroups in 167 JIA patients. Etanercept (105, 62.9%), adalimumab (28, 16.8%), and infliximab (21, 12.6%) were the most prescribed first-line biologic drugs. Secondary failure was the most common reason for the treatment changes among 42 (43.3%) patients, followed by non-life-threatening side effects in 12 (12.4%) and primary failure in 11 (11.3%). Polyarticular JIA showed higher HAQ (p = 0.020) and DAS28-ESR (p < 0.001) before biologics and had a longer disease duration to initiation of biologic treatment than enthesitis-related arthritis (p < 0.001). Only one patient (1.2%) in the enthesitis-related arthritis group needed the hip prosthesis, while 12 patients (18.5%) in the polyarticular JIA group required the same procedure (p < 0.001). In adult rheumatology departments, the most common JIAs present with ongoing disease are enthesitis-related arthritis and polyarthritis. Secondary failure was the main reason nearly half of the patients needed biologic changes during follow-up. The polyarticular group appears to have a higher disease severity and level of disability. Key Points • The most of juvenile idiopathic arthritis patients in adult rheumatology clinics require biologics are enthesitis-related arthritis and polyarticular arthritis. • Approximately half of the patients require biologic changes during follow-up, most of these due to secondary failure. • Disease severity and disability appear to be higher in the polyarticular group, therefore treatment intensification may be considered.

BackgroundWe aim to assess the efficacy, safety and tolerability of DTG+3TC as a switch regimen after 10 years of its introduction in clinical practice.MethodsAn observational study was conducted with virologically suppressed PLWH switching to DTG+3TC in a multicenter cohort. Exclusion criteria included HBsAg+ status and M184V resistance mutation. We employed Kaplan-Meyer survival analysis for virological failure (VF) and treatment discontinuation (TD), Cox-regression for VF or TD predictors, and linear mixed models for immunological and metabolic parameter changes.ResultsWe enrolled 2430 PLWH: 1587 (65.3%) were males, with a median age of 54.5 yrs. Full population characteristics are shown in Table1.During 9199 PYFU, we observed 82 VF (0.9 per 100 PYFU); no emergent resistance mutations were registered among VF. Estimated probabilities of maintaining virological suppression (VS) at 240 and 480 wks were 96.2% and 92.8%, respectively. At a multivariate analysis, a history of at least one previous VF before switch (vs no event, aHR 2.09, p=0.005) and a time of VS < 8 years before switch (vs VS > 8 years, aHR 1.82, p=0.021) were significantly associated with a higher risk of VF.During 9287 PYFU, we observed 339 TD (3.7 per 100 PYFU). Estimated probabilities of maintaining DTG/3TC were 83.8% at 240 wks and 79.4% at 480 wks. Discontinuations for toxicity were 78 (23.0% of all TD), with CNS toxicity accounting for 25 cases. Other frequent reasons for TD were: switch to CAB+RPV (64, 18.9%) and treatment intensification (32, 9.4%).At a multivariate analysis, we found that a HIV-RNA peak > 500.000 cps/mL (aHR 1.55, p=0.006) and the presence of HBcAb (aHR 1.60, p=0.002) were significantly associated with a higher risk of TD; meanwhile, the presence of DTG in the ARV regimen before switch, (aHR 0.51, p=0.001) was inversely correlated with TD risk.After 240 weeks, we registered a significant improvement in both CD4+ count (+59, p < 0.001) and CD4/CD8 ratio (+0.1, p < 0.001).As to metabolic parameters, we observed significant improvement in total cholesterol, tryglicerides and HDL cholesterol at both 240 and 480 weeks (p < 0.02 for all).ConclusionWe assessed the efficacy and safety of DTG+3TC in the long term while also showing neutral impact on metabolic parameters.DisclosuresAll Authors: No reported disclosures

The benefit of treatment intensification in metastatic colorectal cancer (mCRC) may be influenced by host-related factors that are not accounted for in clinical trials or standard care. We investigated the prognostic and predictive value of muscle-bone ratio (MBR), a sarcopenia marker automatically derived from computed tomography (CT) images, in mCRC patients from the prospective PanaMa study and a real-world validation cohort. PanaMa (AIO KRK 0212; NCT01991873) randomized patients with RAS wild-type mCRC, following induction therapy, to maintenance therapy with fluorouracil and folinic acid (FU/FA) with or without panitumumab (Pmab). MBR was automatically calculated from baseline CT images using a validated deep learning model, and patients were stratified by MBR tertiles. Associations with progression-free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier and Cox regression analyses. A retrospective real-world cohort of mCRC patients treated with cetuximab was used for validation. Pre-maintenance CT images were available for 189 of 248 randomized patients (76.2%) from PanaMa. In patients receiving FU/FA+Pmab, high MBR was associated with longer PFS (HR 0.43, 95% CI: 0.25-0.73, P=0.002) and OS (HR 0.41, 95% CI: 0.21-0.77, P=0.006), while no association was observed in patients receiving FU/FA alone. Pmab provided a PFS benefit only in patients with high MBR (HR 0.42, 95% CI: 0.24-0.73, P=0.002). The association of high MBR with superior PFS (P=0.002) and OS (P<0.001) was confirmed in the real-world cohort. The benefit of anti-EGFR therapy in mCRC is confined to patients with high MBR. Automated sarcopenia assessment holds promise for personalized treatment intensification in mCRC.

The impact of endoscopic sinus surgery (ESS) extent on long-term disease control and therapeutic escalation in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. This study aims to evaluate the clinical applicability of endoscopy-based criteria for therapeutic escalation and to determine the impact of surgical extent on the risk and timing of treatment intensification. A retrospective cohort study with 3-year follow-up was conducted. CRSwNP patients who underwent ESS were included and classified according to Lamella Ostium Extent Mucosa (LOEM) system (t1-t4). Baseline characteristics and disease severity measures were assessed. Therapeutic escalation was defined by endoscopic criteria. Predictors of escalation and the effect of ESS extent on escalation timing across clinical phenotypes were analyzed using multivariate logistic regression, Kaplan-Meier curves and Cox regressions. In the overall sample (n=172), patients who required escalation showed higher SNOT-22 scores and poorer olfactory function. More extensive ESS (LOEM t3-t4) was associated with significantly reduced escalation risk and prolonged disease control. Post hoc analyses confirmed significant pairwise differences favoring extensive (t3-t4) over limited (t1-t2) surgery. Subgroup analyses demonstrated greater benefits in older subjects, atopic patients, revision surgeries and patients with eosinophils &gt;300cells/μL. Higher baseline SNOT-22 scores remained an independent predictor of escalation after ESS. Surgical extent appears to influence both escalation risk and timing. More extensive ESS may provide more sustained control, particularly in revision cases and biomarker-defined subgroups, supporting its integration into personalized algorithms.

Despite curative surgery and adjuvant chemotherapy, a significant number of early stage I to II ovarian cancers relapse. The CA125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor intrinsic chemosensitivity in advanced epithelial ovarian cancer. We assessed the prognostic value of KELIM in patients with early-stage ovarian cancer, with respect to 5-year recurrence-free survival and overall survival, using the Meta-Analysis in Ovarian Cancer, which is the Gynecologic Cancer InterGroup individual patient-data meta-analysis of randomized trials evaluating different adjuvant chemotherapy regimens. Individual patient KELIM values were previously estimated in 5884 patients from the Meta-Analysis in Ovarian Cancer. The prognostic value of KELIM was assessed using univariable & multivariable analyses in patients with resected International Federation of Gynecology and Obstetrics stage I and II disease. Overall, 1143 patients were identified, including clear cell (46.7%); serous (23.7%); endometrioid (12.4%); and mucinous carcinomas (3.9%). In multivariable analyses, a favorable KELIM score (≥1.0) was associated with higher 5-year recurrence-free survival (68.3% vs 55.9%; HR 0.61, 95% CI 0.48 to 0.77) and 5-year overall survival (80.7% vs 72.8%; HR 0.50, 95% CI 0.36 to 0.68), as was the histological sub-type. In exploratory analyses, KELIM score was a prognostic factor regarding 5-year recurrence-free survival and overall survival across all sub-types (especially clear cell carcinoma and serous, with HR ranging from 0.45 to 0.63) with baseline CA125 ≥15 IU/L, except for mucinous histology. The pragmatic KELIM score is an independent prognostic factor in patients with a non-mucinous stage I to II ovarian cancer optimally resected and treated with adjuvant chemotherapy. KELIM may help identify the patients at higher risk of relapse and death requiring closer follow-up or treatment intensification.

Combining cisplatin and gemcitabine (CG) in the concurrent and adjuvant treatment phase of advanced cervical cancer has improved oncological outcome at the cost of excess toxicity. We aimed to investigate the feasibility and safety of this treatment intensification in the era of modern radiotherapy. A retrospective review was performed on patients treated with definitive chemoradiation including CG for advanced cervical cancer. Treatment consisted of chemoradiotherapy (weekly cisplatin 40 mg/m² and gemcitabine 125 mg/m² with volumetric-modulated arc therapy) followed by image-guided adaptive brachytherapy and 2 cycles of adjuvant CG. Fifty-five patients were included with a median follow-up of 48 months (range, 7-130). Patients with FIGO stage IIIC1 accounted for 49.1% of cases, with an additional 23.6% being stage IIIC2. The median number of concurrent gemcitabine and cisplatin administrations was 4 (range, 1-6), and 5 (range, 2-8), respectively. Forty-four patients (80%) received adjuvant chemotherapy. Hematological severe short-term toxicity (grade ≥3) occurred in 22 patients (43.1%). There was no deviation from planned radiotherapy-schedule. No treatment-related death occurred. Five patients experienced late grade ≥3 adverse events. Local, locoregional and distant control rates at 5 years were 82.0%, 70.5% and 69.3%, respectively. Five-year progression-free survival was 50.9% and overall survival was 70.9%. Concurrent chemoradiation with CG followed by image-guided adaptive brachytherapy and adjuvant CG is feasible and associated with a lower toxicity profile than previously reported. Further research is needed to refine patient selection for different treatment intensification strategies in advanced cervical cancer.

Association between rheumatoid arthritis flares and joint structural changes at 24 months: using FLARE-RA questionnaire.

Worldwide, the elderly population is steadily growing. A new population of very elderly patients is emerging, with specific management requirements, particularly at the end of life. However, data is scarce concerning the end-of-life care in these patients. The territories where this population is growing rapidly, like overseas France, was therefore of the utmost interest, to describe how they are provided end-of-life care and die.The aim of the study was to describe end-of-life care and death in overseas France nonagenarians and over, and to compare them with the rest of the population in these territories. A retrospective study of a representative sample of adult patients who died between March 2020 and February 2021 was conducted in overseas France. Physicians who certified the deaths were asked to describe end-of-life care and medical decisions in a questionnaire. A total of 1815 deaths were analysed over 8730 questionnaires sent, with a total of 1082 questionnaires collecting data on non-sudden informed deaths. The nonagenarians were mostly women (p<0.0001) with cognitive impairment (p<0.0001) and died at home (p < 0.0001). Physicians were mostly experienced (p=0.0022) general practitioners (p<0.0001). Nonagenarians were less provided with palliative care than the rest of the population (64.36% vs 74.83%), with a lower use of deep and continuous sedation maintained until death (2.84%vs 15.19%) and less intensification of treatments to relieve symptoms (23.45%vs 32.56%). The population of nonagenarians was specific in causes of death and comorbidities. Improving end-of-life care for these patients can include a high access to specialist palliative care and symptoms management.

BackgroundKawasaki disease (KD) is the leading cause of acquired childhood heart disease, with untreated cases progressing to giant coronary artery aneurysms (GCAAs) in 2-3% of patients. While outcomes are well-documented in high-income settings, data from low- and middle-income countries (LMICs) remain limited. This study examines clinical profiles, treatment responses, and outcomes of children with GCAAs managed at a tertiary care center in South India.MethodsWe conducted a retrospective review of 18 children with KD-associated GCAAs (z-score >10 or diameter >8mm) treated between 2019-2024 at a tertiary care center in Kerala, India. All patients were referred from external centers with documented IVIg resistance. Treatment intensification included infliximab, corticosteroids, cyclosporine, and anakinra. Primary outcome was GCAA dimension change at last follow-up; secondary outcomes included thrombotic events, mortality, and anticoagulation cessation.ResultsThe cohort comprised predominantly of males (n = 14, 77.8%) with median symptom onset at 1.1 (IQR 0.3 – 2.7) years; 50% were under one year old. While ten children (55%) experienced delayed diagnosis (>10 days after symptom onset) with median diagnosis at 11 (IQR 7 – 13.5) days; all faced delays in treatment intensification. Excluding two children lost-to-follow-up, during the median follow-up of 8.6 (5.2 – 19.4) months, complete GCAA resolution occurred in three (18.8%), reduction to small/medium aneurysms in six (37.6%), while five (31.3%) remained static. One mortality (6.3%) from myocardial infarction and a patient requiring coronary artery bypass grafting were observed. Anticoagulation was discontinued in 56.25% of children whose aneurysms resolved or reduced significantly.ConclusionDelayed diagnosis and treatment intensification may have contributed to mixed outcomes in this GCAA cohort. Early recognition, appropriate risk stratification, and timely immunosuppression intensification are essential to improve prognosis and reduce severe coronary complications in resource-limited settings.

The involvement of inflammation in the development of ulcerative colitis (UC) is significant. Therefore, the purpose of our study was to evaluate the serum levels of selected cytokines, chemokines and growth factors in children at the time of diagnosis/exacerbation of UC (T0), as well as 3 (T1) and 6 (T2) months after the introduction or change of treatment, and to assess their usefulness in predicting the course of the disease and the need for treatment intensification. Thirty-three children (study group) with UC, including 25 with new diagnoses of UC (ndUC), and 29 healthy controls (Ctr) were included in the study. Serum cytokine panels were measured at three time points: T0, T1, and T2 using multiplex ELISA method. At T0, significantly higher levels of IL-8, IL-17, eotaxin, and granulocyte colony-stimulating factor (G-CSF) were observed in both the UC and ndUC groups. At T1, higher levels of IL-17, eotaxin, and fibroblast growth factor (FGF) were noted in the study group compared to controls. When the group was stratified according to clinical activity at 6 months, IL-17, eotaxin, and FGF levels at T0 were higher in patients who achieved Pediatric Ulcerative Colitis Activity Index (PUCAI) < 10 compared to those with PUCAI ≥ 10. However, these associations should be interpreted with caution due to the heterogeneity of treatment interventions, which likely influenced the outcomes. Our exploratory analyses indicate that serum cytokines may reflect disease activity and may help in understanding clinical outcomes in pediatric UC, although prospective studies with standardized treatment protocols are needed to confirm their predictive value.

As routinely collected longitudinal data becomes more available in many settings, policy makers are increasingly interested in the effect of time-varying treatments (sustained treatment strategies). In settings such as this, many commonly used statistical approaches for estimating treatment effects, such as g-methods, often adopt the 'no unmeasured confounding' assumption. Instrumental variable (IV) methods aim to reduce biases due to unmeasured confounding, but have received limited attention in settings with time-varying treatments. This paper extends and critically evaluates a commonly used IV estimating approach, Two Stage Least Squares (2SLS), for evaluating time-varying treatments. Using a simulation study, we found that, unlike standard 2SLS, the extended 2SLS performs relatively well across a wide range of circumstances, including certain model misspecifications. We illustrate the methods in an evaluation of treatment intensification for Type-2 Diabetes Mellitus, exploring the exogeneity in prescribing preferences to operationalise a time-varying instrument.

B-cell acute lymphoblastic leukaemia (B-ALL) in adolescents and adults remains challenging due to high relapse rates and suboptimal outcomes. Although minimal residual disease (MRD) and cytogenetic risk classification are independent prognostic indicators for B-ALL in adolescents and adults, their combined utility remains under explored. This retrospective study analysed 609 adolescent and adult patients with B-ALL to evaluate the integrated prognostic value of MRD at end of induction (MRD1) and after first consolidation (MRD2), combined with cytogenetic risk stratification (standard risk [SR] vs. poor risk [PR]). Although cytogenetic risk alone was not an independent prognostic factor, MRD positivity at either time point significantly predicted inferior 5-year RFS and OS in PR patients. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) improved outcomes overall; however, PR patients with MRD2 positivity remained at high risk of relapse post-transplant. Multivariate analysis identified MRD1 and MRD2 as independent predictors of both relapse (RFS HR = 2.048) and mortality (OS HR = 1.979) in PR patients (all p < 0.01). These results demonstrate that combining MRD assessment with cytogenetic risk improves risk stratification, precisely identifying poor-risk patients with persistent MRD who may benefit from treatment intensification, including novel strategies post-transplant.

Several liquid-, and tissue-based markers are available to guide primary diagnosis-, active surveillance-, and treatment-related decision-making for patients with prostate cancer. Most of these tests can improve the balance of harms and benefits associated with early detection, and aid patient selection for treatment intensification. However, the costs of these tests can make their integration in routine clinical practice challenging. To date, prostate-specific antigen (PSA) is still one of the most well-known and widely utilized tumor markers worldwide, with a unique facility ranging from the diagnosis to the treatment-related follow-up of patients with prostate cancer. Future research efforts are needed to integrate biomarkers and novel imaging techniques, such as prostate magnetic resonance imaging, in the decision-making pathways. Despite the growing body of knowledge and evidence, considerable challenges remain in optimizing risk-stratification, improving patient selection and cost-efficacy in different prostate cancer (PCa)-related settings.

Therapeutic inertia is a key barrier to blood pressure (BP) control. To identify demographic, clinical, and health system factors associated with treatment intensification for uncontrolled hypertension including in-person medical office versus team-based BP clinic encounters. This mixed-methods study included a quantitative analysis of electronic health records and 11 semi-structured provider interviews from Kaiser Permanente Southern California (KPSC). This study included KPSC adults with hypertension and uncontrolled BP (≥ 140/ ≥ 90mm Hg) during office encounters in 2018, followed for 6months. Treatment intensification defined as increasing dose or adding a new class of antihypertensive medications, and 6-month BP reduction associated with treatment intensification. Multivariable regression analyses were used to identify factors associated with treatment intensification. Themes around barriers and facilitators of treatment intensification were developed from the provider interviews. Among 221,519 patients with uncontrolled BP, 29% received an increased dose or added medications. Mean (SD) 6-month systolic BP reductions were 16.6 (14.3) mm Hg and 11.7 (13.5) mm Hg for those with treatment intensification versus not (p < 0.01). Older age (OR for age ≥ 76 vs 18-55years = 0.68; 95% CI 0.65, 0.71) and having diabetes (OR = 0.86; 95% CI 0.84, 0.88) were associated with lower odds of treatment intensification; while team-based BP clinic encounters were associated with higher odds of treatment intensification (OR = 1.23; 95% CI 1.20, 1.27). Provider interviews showed concerns about side effects, medication nonadherence, and shared decision-making are key factors in decisions to intensify therapy. Less than one-third of patients with uncontrolled BP received increased hypertension medication doses, with more frequent intensifications in team-based BP clinics. Targeted interventions to address the identified barriers are needed to improve BP control.

Immunotherapy in the upfront definitive management of locally advanced cervical cancer: An evolving treatment paradigm.

BackgroundTherapeutic inertia the failure to intensify treatment despite persistent hyperglycemia is a major barrier to optimal management of type 2 diabetes, particularly in low-resource settings.MethodsA hospital-based cross-sectional study was conducted from June 1, 2024, to August 30, 2024. A total of 299 systematically selected patients were included. Data were collected via structured questionnaires and patient medical records. Bivariable and multivariable binary logistic regression analyses were used to identify factors associated with therapeutic inertia. Variables with a p value < 0.25 in the bivariable analysis were included in the multivariable model, and those with a p value < 0.05 were considered statistically significant.ResultsOverall, 67.2% of patients experienced therapeutic inertia. Multivariable analysis identified four independent predictors: lack of health insurance reduced the likelihood of treatment intensification (AOR = 0.177; 95% CI: 0.054–0.576; p = 0.004); management by general practitioners doubled the odds of inertia compared with specialist care (AOR = 2.002; 95% CI: 1.017–3.939; p = 0.045); higher baseline fasting plasma glucose was associated with increased odds of inertia (AOR = 1.008; 95% CI: 1.003–1.013; p = 0.003); and limited availability of point-of-care HbA1c testing substantially increased the risk of inertia (AOR = 8.423; 95% CI: 1.889–37.561; p = 0.005).ConclusionTherapeutic inertia is highly prevalent, affecting 67.2% of ambulatory patients with type 2 diabetes at NEMMCSH. This study highlights critical barriers at patient, provider, and system levels. Interventions such as expanding insurance coverage, enhancing provider training and decision support, implementing prompts for elevated glycemia, and integrating point-of-care HbA1c testing are urgently needed to reduce therapeutic inertia and improve glycemic control in resource-constrained settings.

The treatment landscape for advanced non-small cell lung cancer (NSCLC) with common EGFR mutations has evolved significantly, with osimertinib established as the first-line standard. Two recent phase III trials, FLAURA2 and MARIPOSA, demonstrated that first-line intensification-through osimertinib plus chemotherapy or amivantamab-lazertinib-significantly prolongs overall survival compared to osimertinib alone. The aim of this review was to critically assess whether treatment intensification should be adopted as a new standard and, if so, in which patients. We identified high-risk subgroups more likely to benefit from upfront combination strategies, such as those with brain or liver metastases, L858R mutations, TP53 co-mutations, or detectable ctDNA. However, the improved efficacy comes with increased rates of grade ≥ 3 adverse events and treatment discontinuation, raising concerns about tolerability and quality of life (QoL), particularly in real-world settings with frailer patients. Post-progression strategies are also evolving and may impact the long-term value of upfront intensification. Emerging approaches, including targeted and untargeted therapies, and novel antibody-drug conjugates (ADCs), offer promising alternatives that may change future treatment options. Careful patient selection, improved toxicity management, and integration of QoL measures will be critical to ensure that the survival advantage demonstrated in trials can translate into true benefit in routine clinical practice. Future research should focus on identifying robust clinical and molecular markers to guide personalized treatment decisions.