Individual Patient-level Data Research Articles

Outcomes of coronary intravascular lithotripsy for the treatment of calcified nodules: a pooled analysis of the Disrupt CAD studies.

Coronary intravascular lithotripsy (IVL) safely facilitates stent implantation in severely calcified lesions. This analysis sought to determine the relative impact of IVL on acute and long-term outcomes specifically in calcified nodules (CNs). Individual patient-level data (N=155) were pooled from the Disrupt CAD optical coherence tomography (OCT) substudies. Severely calcified lesions with and without CNs were compared by OCT for acute procedural results and for target lesion failure (TLF) at 2 years - a composite of cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation. A CN was identified in 18.7% (29/155) of lesions. When comparing lesions with and without CNs, there were no significant differences in preprocedure minimal lumen area or diameter stenosis; however, the mean calcium angle and calcium volume were greater in CN lesions. Despite a higher calcium burden, the final minimal stent area (CN: 5.7 mm2 [interquartile range [IQR] 4.4, 8.3] vs non-CN: 5.7 mm2 [IQR 4.7, 7.2]; p=0.80) and stent expansion (CN: 79.3% [IQR 64.3, 87.0] vs 80.2% [IQR 68.9, 92.4]; p=0.30) were comparable between the two groups. In the CN group, the final stent area and expansion at CN sites were 7.6 mm2 (IQR 5.5, 8.5) and 89.7% (IQR 79.8, 102.5), respectively. The cumulative incidence of TLF at 2 years was 13.9% and 8.0% in the CN and non-CN groups, respectively (p=0.32). Despite a greater calcium volume in CNs, IVL use was associated with comparable stent expansion and luminal gain in both CN and non-CN lesions. Further studies powered for clinical outcomes comparing different plaque modification techniques in this lesion subset are warranted.

Association Between Baseline Driving Pressure and Mortality in Very Old Patients with Acute Respiratory Distress Syndrome.

Rationale: Because of the effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age. Objectives: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (⩾80 yr), patients. Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor and 90-day mortality as the dependent variable. Measurements and Main Results: On the basis of data from 4,567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (P = 0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and nonsurvivors significantly changed across the adult lifespan (P < 0.01). In both cohorts, a driving pressure threshold of 11 cm H2O was associated with mortality in very old patients. Conclusions: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on the mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.

Laser interstitial thermal therapy for cavernous malformations: a meta-analysis of individual patient-level data.

Several case series have investigated the use of laser interstitial thermal therapy (LITT) to treat cavernous malformations (CMs), for either seizure control or reduction of neurological symptoms and future hemorrhage risk. However, pooled outcomes are largely unknown. The authors aimed to quantify posttreatment seizure freedom, symptomatic progression or hemorrhage, perioperative complications, and imaging outcomes from the available literature. This study was a PRISMA-compliant systematic review and individual patient-level data meta-analysis of studies reporting LITT ablation of CMs. For patients with epilepsy, the pooled Engel seizure freedom rate was calculated. The rate of symptomatic progression or hemorrhage was calculated for all patients. Fixed-effects logistic regression models were used to test for predictors of seizure freedom and postoperative complications. Linear regression models were used to obtain pooled estimates of the percent CM volume ablated. A total of 39 patients (28 with epilepsy) underwent LITT for the treatment of 45 CMs (37 cortical, 8 subcortical) at six centers. Among patients with epilepsy, 88.0% (95% CI 68.7%-96.1%) were seizure free at the last follow-up (median 30.0 months, range 12.0-49.0 months). Six patients (15.4%) experienced immediate postoperative neurological deficits. No perioperative hemorrhage was reported, and no patients experienced subsequent hemorrhage or symptomatic progression during follow-up (median 26.0 months, range 2.0-53.0 months). There was no difference in the odds of seizure freedom or adverse events based on preoperative characteristics. Nonepileptogenic CMs (mean volume 2.5 cm3) were significantly larger than epileptogenic CMs (mean volume 0.8 cm3; p = 0.002). LITT was associated with a mean CM volume reduction of 73.7% (95% CI 64.1%-83.2%, p < 0.0001) for epileptogenic CMs and 53.8% (95% CI 14.2%-93.3%, p < 0.023) for nonepileptogenic CMs (p = 0.14). LITT is a promising therapy for CMs with the goal of seizure control or prevention of symptomatic progression or hemorrhage. While there is a notable risk of immediate postablation neurological deficit, most were transient and nondisabling, and this risk must be weighed against that of continued observation or open resection. Considering the limited number of studies, small number of patients, and limited follow-up time available, additional experience and research with larger patient cohorts and longer-term follow-up will be necessary to validate these findings.

Ponatinib vs. asciminib in post-second-generation tyrosine kinase inhibitor therapy for chronic-phase chronic myeloid leukemia: a matching-adjusted indirect comparison.

Ponatinib and asciminib are approved for third-line therapy in chronic-phase chronic myeloid leukemia (CP-CML) and are the only drugs approved for patients with the T315I mutation in the United States. In Europe, only ponatinib is approved for patients with the T315I mutation. Clinical trials evaluating ponatinib or asciminib in patients with relapsed and refractory (R/R) CP-CML who failed one or more second-generation TKIs or had the T315I mutation were identified in a systematic review of medical literature databases. A matching-adjusted indirect comparison (MAIC) analysis with individual patient-level data with ponatinib was used to balance baseline characteristics between ponatinib and asciminib groups. After matching, the response rate was calculated using the MAIC weight for each patient and the difference in response rate was calculated using a two-independent proportion Z-test. Cumulative rates of BCR::ABL1 IS ≤1% and major molecular response (MMR) in patients without baseline response were compared. Patients were further stratified by T315I mutation status. The MAIC included four trials (ponatinib: NCT02467270, NCT01207440; asciminib: NCT02081378, NCT03106779). In patients without baseline response of BCR::ABL1 IS ≤1%, the adjusted BCR::ABL1 IS ≤1% rate difference with ponatinib vs. asciminib was 9.33% (95% confidence interval [CI]: 0.79%-17.86%; adjusted MMR rate difference: 6.84% [95% CI: -0.95%-14.62%]) by 12 months in favor of ponatinib. In patients with the T315I mutation, adjusted BCR::ABL1 IS ≤1% rate difference with ponatinib vs. asciminib was 43.54% (95% CI: 22.20%-64.87%; adjusted MMR rate difference: 47.37% [95% CI: 28.72%-66.02%]) by 12 months. After key baseline characteristics adjustment, cumulative BCR::ABL1 IS ≤1% and MMR rates were statistically higher with ponatinib than asciminib in patients without a baseline response in most of the comparisons by 12 months. Favorable efficacy outcomes observed in ponatinib vs. asciminib were consistently stronger in the T315I mutation subgroup.

Computational and Human Intelligence Methods for Constructing Practical Risk Prediction Models: An Application to Cardio-Renal Outcomes in Non-Diabetic CKD Patients

The current investigation aimed to develop a novel approach for risk prediction modeling of clinical outcomes in common diseases based on computational and human intelligence techniques with no a priori input on risk factors using real-world individual patient-level data from administrative claims. Bootstrapping multivariable Cox regression and ant colony optimization were employed to develop time-to-first-event risk prediction models of cardio-renal outcomes in patients with non-diabetic chronic kidney disease (CKD) as a demonstration case. A cohort of 504,924 non-diabetic CKD stage 3 or 4 patients enrolled from 2008 to 2018 were identified in the US administrative de-identified claims database, Optum Clinformatics® Data Mart. Initial set of potential risk factors was derived from patient-level data at baseline and included more than 540,000 variables. Risk prediction models of hospitalization for heart failure, worsening of CKD stage from baseline and a renal composite outcome of end-stage kidney disease, kidney failure or need for dialysis in non-diabetic CKD stage 3 or 4 were built. Final model optimization was conducted using human intelligence to combine clinically similar features and build equivalence classes to ensure that risk factors included in the final model were routinely collected and easily interpretable by healthcare providers. Demonstrated validity of our approach in non-diabetic CKD offers opportunities for application in other therapeutic areas, with the potential to improve overall prognosis and decrease the clinical and economic burden of common diseases. The approach enables developing practical prediction models for risk estimation in routine clinical practice.

Characteristics and outcomes in patients with lenalidomide-refractory multiple myeloma treated with 1-3 prior lines of therapy: analysis of individual patient-level data from daratumumab clinical trials

BackgroundThe introduction of proteasome inhibitors (PIs) and lenalidomide as treatment for newly diagnosed multiple myeloma (MM) has led to an increased population of lenalidomide-refractory patients. Limited data are available characterizing current treatments and outcomes in this difficult-to-treat population. MethodsIndividual patient-level data were analyzed from the treatment arms of multiple daratumumab studies, including APOLLO, CASTOR, CANDOR, EQUULEUS, ALCYONE, MAIA, GRIFFIN, POLLUX, and CASSIOPEIA. Included patients were PI exposed and lenalidomide refractory, received 1–3 prior lines of therapy (LOT), and had an Eastern Cooperative Oncology Group performance status <2. Treatments and outcomes were analyzed by number of prior LOT in the lenalidomide-refractory population. Time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method. FindingsOut of 4764 patients, 915 patients (prior LOT, one [n=114]; two [n=462]; three [n=339]) met inclusion criteria. Median follow-up was 29.7 months (range 28·0–31·7). The overall response rate was 55·4%. Estimated median TTNT was 9·7 months, median PFS was 10.0 months, and median OS was 27·5 months. Response rates and PFS decreased as number of prior LOT increased. Prognostic factors for response, TTNT, PFS, and OS included International Staging System stage, baseline plasmacytoma status, baseline hemoglobin, anti-CD38–refractory status, and cytogenetic risk status. InterpretationLenalidomide-refractory patients treated with 1–3 prior LOT have poor PFS and OS, which generally worsen with each additional LOT, highlighting the need for new and effective treatments for this population.

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-Analysis Based on Individual Patient-Level Data of Randomized Trials.

While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p =0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs nal-IRI plus 5-FU/LV, 95% CI 0.93-2.07, p=0.11) and 1.36 (mFOLFIRI vs nal-IRI plus 5-FU/LV, 95% CI 0.92-2.03, p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Epidemiology and regional variance of traumatic peripheral nerve injuries in Sweden: A 15-year observational study.

Traumatic peripheral nerve injuries pose significant challenges to healthcare systems and individuals, affecting sensory function, causing neuropathic pain, and impairing quality of life. Despite their impact, comprehensive studies on the epidemiology and regional variance of these injuries are scarce. Understanding the incidence, trends, and anatomical distribution of such injuries is essential for targeted interventions and resource allocation. This observational study utilized register-based data from the Swedish National Patient Register covering the period from 2008 to 2022. Incidence rates, trends, and anatomical distribution of traumatic peripheral nerve injuries were analyzed using descriptive statistics, Poisson regression modeling, and regional comparisons. Higher incidences of peripheral nerve injuries were observed among men compared to women across all age groups. The hand and wrist were the most commonly affected sites. Regional variations in incidence rates were evident, with some regions consistently exhibiting higher rates compared to others. Notably, a decreasing trend in injuries was observed over the study period. This study underscores the importance of targeted interventions and preventive strategies, considering sex, age, and regional disparities. Further research incorporating individual patient-level data is warranted to enhance our understanding and inform tailored interventions to reduce the burden of these injuries.

Complications of button battery ingestion or insertion in children: a systematic review and pooled analysis of individual patient-level data.

Button battery (BB) exposures are common in children and can have devastating consequences. We reviewed current evidence on the complications associated with BB exposure and identified predictors of outcomes using individual patient-level data. We carried out a systematic review and pooled analysis by searching MEDLINE, Embase, and Scopus up to May 19, 2023. Included studies describe complications following BB exposures in children (aged < 18years). Odds ratios (ORs) were calculated using binary logistic regression to measure associations between predictive factors and different outcomes. Two-hundred seventeen studies (439 children) were included. The median age at presentation was 1.75 [interquartile range (IQR) 1.00-3.00] years and 399 (90.9%) exposures were ingestions. Of the 380 cases reporting sex, 162 (42.6%) were female. Feeding (192, 48.1%) and respiratory difficulties (138, 34.6%) were common presenting features for ingestions, while symptomatology was site-specific for insertions. Common complications included oesophageal mucosal damage alone (105, 26.3%) and tracheooesophageal fistula (93, 23.3%) for ingestions, and nasal septal perforation (22, 55.0%) and mucosal damage alone (13, 32.5%) for insertions. Intestinal perforation occurred in 2.5% of ingestion cases, including perforation of Meckel's diverticulum, peritonitis, and jejunocolic fistula. Vascular complications were common among children who died. Age (≤ 2years), battery exposure duration (> 6hours), and battery diameter (≥ 20mm) were associated with common and severe complications of ingestions. BB injuries are time-critical, with severe sequelae predominantly affecting young children. Diagnosis is challenging. Preventative work through regulation and safer battery design are required to eliminate this problem.

Clinical manifestation and outcome of lung cancer patients with ocular metastasis: 16 case reports and systematic review.

Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual-level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127-5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391-7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675-11.099) were significantly associated with overall survival. For non-SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087-0.651) and combined therapy (HR, 0.133; 95% CI, 0.017-0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new-generation tyrosine kinase inhibitors (TKIs) are preferred.

Matching-adjusted indirect comparison of talquetamab vs selinexor-dexamethasone and vs belantamab mafodotin in patients with relapsed/refractory multiple myeloma

Objective Talquetamab is the first GPRC5D-targeting bispecific antibody approved for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). This matching-adjusted indirect comparison (MAIC) study was conducted to compare the effectiveness of talquetamab vs selinexor-dexamethasone (sel-dex) and vs belantamab mafodotin (belamaf) in patients with TCE RRMM. Methods An unanchored MAIC was performed using individual patient-level data from patients treated with subcutaneous talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W) from MonumenTAL-1 (NCT03399799/NCT04636552) and published summary data for sel-dex from STORM (NCT02336815) and belamaf from DREAMM-2 (NCT0325678). Patients from MonumenTAL-1 who met key eligibility criteria for STORM and DREAMM-2 were included. Outcomes of interest were overall response rate (ORR), complete response or better (≥CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results After adjustment for cross-trial differences, patients treated with both dosing schedules of talquetamab showed significantly better ORR, ≥CR, and DOR vs sel-dex and significantly higher ORR and ≥ CR vs belamaf; DOR was relatively similar to belamaf. PFS was significantly improved with talquetamab Q2W and numerically in favor of talquetamab QW vs sel-dex and significantly improved with both dosing schedules of talquetamab vs belamaf. OS was significantly improved with both dosing schedules of talquetamab vs sel-dex and was numerically in favor of both dosing schedules of talquetamab vs belamaf. Conclusion These analyses show superior effectiveness of both talquetamab dosing schedules vs sel-dex and vs belamaf for most outcomes and highlight talquetamab as an effective treatment option for patients with TCE RRMM.

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Complete Versus Culprit-Only Revascularization in Older Patients With ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis.

Complete revascularization is the standard treatment for patients with ST-segment-elevation myocardial infarction and multivessel disease. The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit (>1 year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in patients with ST-segment-elevation myocardial infarction ≥75 years of age enrolled in randomized clinical trials investigating complete versus culprit-only revascularization strategies. PubMed, Embase, and the Cochrane database were systematically searched to identify randomized clinical trials comparing complete versus culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary end point was death, myocardial infarction, or ischemia-driven revascularization. The secondary end point was cardiovascular death or myocardial infarction. Data from 7 randomized clinical trials encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization) were analyzed. The median age was 79 [interquartile range, 77-83] years. Of the patients, 595 (34%) were female. Follow-up ranged from a minimum of 6 months to a maximum of 6.2 years (median, 2.5 [interquartile range, 1-3.8] years). Complete revascularization reduced the primary end point up to 4 years (hazard ratio, 0.78 [95% CI, 0.63-0.96]) but not at the longest available follow-up (hazard ratio, 0.83 [95% CI, 0.69-1.01]). Complete revascularization significantly reduced the occurrence of cardiovascular death or myocardial infarction at the longest available follow-up (hazard ratio, 0.76 [95% CI, 0.58-0.99]). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. In this individual patient data meta-analysis of older patients with ST-segment-elevation myocardial infarction and multivessel disease, complete revascularization reduced the primary end point of death, myocardial infarction, or ischemia-driven revascularization up to 4 years. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or myocardial infarction but not the primary end point. URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022367898.

Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association. Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS. Methods: Individual patient-level data from five large phase III randomized controlled trials (RCTs) was utilized to investigate the association of both age and disease duration with annualized relapse rate (ARR), contrast-enhancing lesions (CELs), and new T2 lesions on magnetic resonance imaging (MRI) at baseline and follow-up. Results: The data set included 5626 participants. Higher age was associated with lower ARRs, lower CEL number on MRI at baseline and follow-up, and lower new T2 lesion numbers at follow-up. This effect was present in all disease duration groups. For example, we found a lower number of new T2 lesions on MRI during follow-up in higher age groups compared to lower age groups, independent of disease duration. Conclusion: Aging in RRMS is associated with a lower risk of inflammatory disease activity, across different disease durations. Age should be taken into account when designing clinical trials and future research should investigate how age should be integrated into personalized predictions of treatment response and risk profiling.

Steering them softly with a quality label? A case study analysis of a patient channelling strategy without financial incentives.

Steering patients to lower priced and/or higher quality providers can increase the value of a healthcare system. In a managed care setting, health insurers may use financial incentives for this purpose. However, introducing cost-sharing differences among providers may cause enrolee discontent, which may result in disenrollment. Simply informing and guiding enrolees to preferred providers without financial incentives may therefore be an attractive alternative for insurers. But the effectiveness of such a soft channelling strategy is unclear. This paper investigates whether a Dutch health insurer's strategy of designating preferred hospitals for breast cancer surgery and for inguinal hernia repair affected its enrolees' hospital choices. In October 2008, preferred hospitals received a quality label ('TopCare') because of their high-quality performances in previous years. The insurer recommended these hospitals to enrolees without a financial incentive. Individual patient-level claims data from the insurer over a 5-year period (2006-2010) and a conditional logit choice model was used. Our study samples for breast cancer surgery and inguinal hernia repair included 7985 and 17,292 patients, respectively. It is found that for both procedures, patients ex ante already had a certain preference for the hospitals designated by the insurer as top-quality providers, even when considering possible additional travel time. Also, for both procedures, patient choice did not differ significantly before and after the launch of the TopCare label. The quality label did not increase patient demand for preferred hospitals. Thus, the insurer's strategy to steer patients to preferred hospital alternatives without a financial incentive was not effective.

Comparative efficacy of ciltacabtagene autoleucel versus idecabtagene vicleucel in the treatment of patients with relapsed or refractory multiple myeloma previously treated with 2–4 prior lines of therapy: a matching-adjusted indirect comparison

Objective To estimate the comparative efficacy of ciltacabtagene autoleucel (cilta-cel) versus idecabtagene vicleucel (ide-cel) in patients with relapsed/refractory multiple myeloma (RRMM) treated with 2–4 prior lines of therapy. Methods Matching adjusted indirect comparison (MAICs) were performed using individual patient-level data (IPD) for cilta-cel from CARTITUDE-1 and CARTITUDE-4 and published aggregated data for ide-cel from KarMMa-3. Cilta-cel patients who met inclusion criteria from KarMMa-3 were selected, and outcomes were compared against data for ide-cel using simulated IPD derived from aggregate-level data from KarMMa-3. Patient characteristics were adjusted by reweighting cilta-cel IPD to match the distribution of prognostic factors in KarMMa-3. Comparative efficacy was estimated for response outcomes using a weighted logistic regression analysis and for progression-free survival using a weighted Cox proportional hazards model. Results Patients treated with cilta-cel were 1.2 times more likely to achieve overall response (relative response ratio [RR]: 1.18 [95% confidence interval: 1.03–1.34]; p = 0.04), 1.3 times more likely to achieve very good partial response or better (RR: 1.34 [1.15–1.57]; p = 0.003), and 1.9 times more likely to achieve complete response or better (RR: 1.91 [1.54–2.37]; p < 0.0001) versus ide-cel patients from KarMMa-3. Cilta-cel was associated with a significant 49% reduction in risk of disease progression or death versus ide-cel (hazard ratio: 0.51 [95% confidence interval: 0.31, 0.84]; p = 0.0078). Conclusion For patients with triple-class exposed RRMM treated with 2–4 prior lines of treatment, cilta-cel was found to provide superior clinical benefit over ide-cel in terms of response and progression-free survival.

Blood pressure variability and prognostic significance in traumatic brain injury: analysis of the eICU-CRD database

BackgroundPreliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI.MethodsWe performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2–7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis.ResultsWe studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18–4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08–4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37–0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32–0.95; ptrend<0.001).ConclusionSystolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Body fat percentage vs body mass index in estimating basal cell carcinoma

BackgroundThe role of body mass index (BMI) in basal cell carcinoma (BCC) risk remains controversial, and limited information is available regarding the relationship between other physical measurements and BCC. Several recent studies have found a positive effect of adiposity on improved survival when obesity was determined solely by BMI (the "obesity paradox"). We hypothesize that body fat percentage (BFP) may serve as a more sensitive risk factor for BCC than BMI. MethodsThe study conducted a retrospective analysis of clinical data from two distinct centers in China. Individual patient-level data were obtained from medical record reviews spanning January 1, 2015, to December 31, 2022. Associations with outcomes were analyzed using univariate and stratified analyses and assessed using multiple logistic regression with adjustment for confounding factors. Additionally, we performed a meta-analysis to further test the observations in our study. ResultsA total of 337 patients, ranging in age from 50 to 91 years, with a mean age of 66.88 (standard deviation 10.16), were included. We observed no significant association between BMI and BCC after adjusting for confounders (OR: 0.71, 95 % CI: 0.36–1.40, P = 0.3186). There was also no convincing effect in a meta-analysis (n = 158,741) (OR: 0.99, 95 % CI: 0.93–1.06, P = 0.8). Furthermore, BFP was found to be associated with BCC (OR: 2.64, 95 % CI: 1.17–5.97, P = 0.0196), supported by strong clinical evidence. ConclusionsOur study supports the hypothesis that BFP is superior to BMI in assessing BCC risk. Multiple logistic regression analyses, coupled with meta-analysis, provided robust evidence that BFP is a sensitive risk factor for BCC, while BMI appears unrelated to risk. According to these findings, routine healthcare practices could benefit from utilizing BFP measurements. The reduction of body fat percentage in low-fat diets may be beneficial for adjuvant treatment of BCC.

The economic burden of cancer, coronary heart disease, dementia, and stroke in England in 2018, with projection to 2050: an evaluation of two cohort studies

Cancer, coronary heart disease, dementia, and stroke are major contributors to morbidity and mortality in England. We aimed to assess the economic burden (including health-care, social care, and informal care costs, as well as productivity losses) of these four conditions in England in 2018, and forecast this cost to 2050 using population projections. We used individual patient-level data from the Clinical Practice Research Datalink (CPRD) Aurum, which contains primary care electronic health records of patients from 738 general practices in England, to calculate health-care and residential and nursing home resource use, and data from the English Longitudinal Study on Ageing (ELSA) to calculate informal and formal care costs. From CPRD Aurum, we included patients registered on Jan 1, 2018, in a CPRD general practice with Hospital Episode Statistics (HES)-linked records, omitting all children younger than 1 year. From ELSA, we included data collected from wave 9 (2018-19). Aggregate English resource use data on morbidity, mortality, and health-care, social care, and informal care were obtained and apportioned, using multivariable regression analyses, to cancer, coronary heart disease, dementia, and stroke. We included 4 161 558 patients from CPRD Aurum with HES-linked data (mean age 41 years [SD 23], with 2 079 679 [50·0%] men and 2 081 879 [50·0%] women) and 8736 patients in ELSA (68 years [11], with 4882 [55·9 %] men and 3854 [44·1%] women). In 2018, the total cost was £18·9 billion (95% CI 18·4-19·4) for cancer, £12·7 billion (12·3-13·0) for coronary heart disease, £11·7 billion (9·6-12·7) for dementia, and £8·6 billion (8·2-9·0) for stroke. Using 2050 English population projections, we estimated that costs would rise by 40% (39-41) for cancer, 54% (53-55) for coronary heart disease, 100% (97-102) for dementia, and 85% (84-86) for stroke, for a total of £26·5 billion (25·7-27·3), £19·6 billion (18·9-20·2), £23·5 billion (19·3-25·3), and £16·0 billion (15·3-16·6), respectively. This study provides contemporary estimates of the wide-ranging impact of the most important chronic conditions on all aspects of the economy in England. The data will help to inform evidence-based polices to reduce the impact of chronic disease, promoting care access, better health outcomes, and economic sustainability. Alzheimer's Research UK.