Therapeutic Advances in Chronic Disease最新文献

Background: Numerous first-line immune checkpoint inhibitors (ICI) were developed for patients with advanced non-small cell lung cancer (NSCLC) lacking driver gene mutations. However, this group consists of a heterogeneous patient population, for whom the optimal therapeutic choice is yet to be confirmed.

Objective: To identify the best first-line immunotherapy regimen for overall advanced NSCLC patients and different subgroups.

Design: Systematic review and Bayesian network meta-analysis (NMA).

Methods: We searched several databases to retrieve relevant literature. We performed Bayesian NMA for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (tr-AEs) with a grade equal or more than 3 (grade ⩾ 3 tr-AEs). Subgroup analysis was conducted according to programed death ligand 1 (PD-L1) levels, histologic type, central nervous system (CNS) metastases and tobacco use history.

Results: For the PD-L1 non-selective patients, sintilimab plus chemotherapy (sinti-chemo) provided the best OS [hazard ratio (HR) = 0.59, 95% confidence interval (CI):0.42-0.83]. Nivolumab plus bevacizumab plus chemotherapy (nivo-bev-chemo) was comparable to atezolizumab plus bevacizumab plus chemotherapy (atezo-bev-chemo) in prolonging PFS (HR = 0.99, 95% CI: 0.51-1.91). Atezo-bev-chemo remarkably elevated the ORR than chemotherapy (OR = 3.13, 95% CI: 1.51-6.59). Subgroup analysis showed pembrolizumab plus chemotherapy (pembro-chemo) ranked first in OS in subgroups of PD-L1 < 1%, non-squamous, no CNS metastases, with or without smoking history, and ranked second in OS in subgroups of PD-L1 ⩾ 1% and PD-L1 1-49%. Cemiplimab and sugemalimab plus chemotherapy ranked first in OS and PFS for squamous subgroup, respectively. For patients with CNS metastases, nivolumab plus ipilimumab plus chemotherapy (nivo-ipili-chemo) and camrelizumab plus chemotherapy provided the best OS and PFS, respectively.

Conclusions: Sinti-chemo and nivo-bev-chemo were two effective first-line regimens ranked first in OS and PFS for overall patients, respectively. Pembro-chemo was favorable for patients in subgroups of PD-L1 < 1%, PD-L1 ⩾ 1%, PD-L1 1-49%, non-squamous, no CNS metastases, with or without smoking history. Addition of bevacizumab consistently provided with favorable PFS results in patients of all PD-L1 levels. Cemiplimab was the best option in squamous subgroup and nivo-ipili-chemo in CNS metastases subgroup due to their advantages in OS.

Background: Medication adherence in Medicare-enrolled older adults with asthma and chronic obstructive pulmonary disease (COPD) before and during the coronavirus disease 2019 (COVID-19) pandemic is unknown.

Objectives: To evaluate medication adherence and determinants of high adherence before and during the COVID-19 pandemic in this population.

Design: Retrospective cohort study.

Methods: The proportion of days covered (PDC) reflected medication adherence from January to July 2019 and from January to July 2020. Patients <65 years of age, with COPD or asthma alone, or with cystic fibrosis were excluded. Paired t tests were used to assess adherence changes. Logistic regression explored association of age, sex, diagnosis of depression, number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, albuterol rescue inhaler fills, oral corticosteroid fills, and having a 90-day supply with high adherence (PDC ⩾ 80%).

Results: This analysis included 989 patients. In this cohort, 61.2% of patients received oral corticosteroids. Over 60% of patients had ⩾3 rescue fills in both 2019 and 2020. Medication adherence to controller medications significantly decreased for all controller medications (p < 0.001) in 2020. In 2019 and 2020, number of controller medication classes and having a 90-day supply were associated with high adherence (p < 0.001). In 2019, variables associated with high adherence also included number of medication-related problems and having ⩾3 albuterol rescue inhalers (p < 0.001).

Conclusion: Medication adherence to controllers significantly decreased during the pandemic among older adults with asthma and COPD. Patients with multiple controller classes and a 90-day supply were more likely to be highly adherent. A 90-day supply of medications should be used to facilitate access to medication during the pandemic. Healthcare professionals should assess medication adherence, resolve the barriers of adherence and medication-related problems to achieve desired clinical outcomes among older adults with both asthma and COPD.

Multiple sclerosis (MS) is the most common non-traumatic cause of disability in young people, with vision loss in the disease representing the second largest contributor to disability. In particular, African-American patients with MS are noted to have lower vision than their Caucasian counterparts. In this review, we examine the disparities in eye diseases in the MS population with our gaps in knowledge and discuss the underlying nature of pathological disparities.

Background: Inferior vena cava (IVC) filters are commonly used intravascular devices designed to prevent fatal pulmonary embolism (PE), maintaining the IVC filter as centered as possible is fundamental for achieving its filtration function.

Objective: This study aimed to characterize the tilt angles of IVC filter between the vascular access of internal jugular vein (IJV) and femoral vein (FV), as well as to identify factors associated with increased or decreased tilt angles between placement and retrieval.

Design: This is a multicenter retrospective study.

Methods: A multicenter retrospective study was conducted from October 2017 to March 2019. The primary outcome was the change in filter tilt between placement and retrieval. The secondary outcome was the identifications of factors associated with increased or decreased tilt angle. Relevant variables were analyzed using t-tests, Chi-square tests, Fisher's exact tests, while multivariate logistic regression analysis was used to determine risk factors.

Results: A total of 184 eligible patients were included in this study. The IJV group had a lower likelihood of tilt angle over 10° at the time of placement compared to the FVs group (0% versus 12.5%, p = 0.040). Among the 171 patients with a mean dwell time of 22.1 days, the IJV group had a higher likelihood of tilt angle over 10° than the FVs group (10.3% versus 2.3%, p = 0.080). The use of FVs access at placement was associated with a higher difference between placement and retrieval filter tilt angles (p < 0.01). Multivariate logistic regression analysis showed that hypertension [odds ratio (OR) 0.668; 95% confidence interval (CI) 0.328-1.358, p = 0.265], cardiologic artery disease (OR 0.537; 95% CI 0.136-2.130, p = 0.377), cerebral venous disease (OR 0.555; 95% CI 0.186-1.651, p = 0.290), filter types (OR 1.624; 95% CI 0.851-3.096, p = 0.141), and IVC filter thrombosis (OR 1.634; 95% CI 0.804-3.323, p = 0.175) were not associated with increased filter tilt angle. Right side (OR 0.434; 95% CI 0.202-0.930, p = 0.032) or bilateral lower extremity deep vein thrombosis (LEDVT) (OR 0.383; 95% CI 0.148-0.995, p = 0.049) were identified as protective factors.

Conclusion: IJV access was associated with a lower filter tilt angle at the time of placement, while FVs access was linked to a higher difference between placement and retrieval tilt angles. Right side or bilateral LEDVT were identified as protective factors against increased IVC filter tilt angle.

Tofacitinib was the first Janus kinase inhibitor to be approved for the treatment of rheumatoid arthritis (RA), and there is a large body of data to inform the efficacy and safety of this drug for patients at different places in their treatment journeys and with diverse demographics and characteristics. Here, we summarize tofacitinib clinical efficacy and safety data from some clinical trials, post hoc analyses, and real-world studies, which provide evidence of the efficacy of tofacitinib in treating patients with RA at various stages of their treatment journeys, and with differentiating baseline characteristics, such as age, gender, race, and body mass index. In addition, we review the safety data available from different patient subpopulations in the tofacitinib clinical development program, real-world data, and findings from the ORAL Surveillance post-marketing safety study that included patients aged ⩾50 years with pre-existing cardiovascular risk factors. The available efficacy and safety data in these subpopulations can enable better discussions between clinicians and patients to guide informed decision-making and individualized patient care.

Background: Evidence on whether long-term exposure to air pollution increases the mortality risk in patients with chronic obstructive pulmonary disease (COPD) is limited.

Objectives: We aimed to investigate the associations of long-term exposure to particulate matter with diameter <10 µm (PM₁₀) and nitrogen dioxide (NO₂) with overall and disease-specific mortality in COPD patients.

Design: We conducted a nationwide retrospective cohort study of 121,423 adults ⩾40 years diagnosed with COPD during 1 January to 31 December 2009.

Methods: Exposure to PM₁₀ and NO₂ was estimated for residential location using the ordinary kriging method. We estimated the risk of overall mortality associated with 1-, 3-, and 5-years average concentrations of PM₁₀ and NO₂ using Cox proportional hazards models and disease-specific mortality using the Fine and Gray method adjusted for age, sex, income, body mass index, smoking, comorbidities, and exacerbation history.

Results: The adjusted hazard ratios (HRs) for overall mortality associated with a 10 µg/m³ increase in 1-year PM₁₀ and NO₂ exposures were 1.004 [95% confidence interval (CI) = 0.985, 1.023] and 0.993 (95% CI = 0.984, 1.002), respectively. The results were similar for 3- and 5-year exposures. For a 10-µg/m³ increase in 1-year PM₁₀ and NO₂ exposures, the adjusted HRs for chronic lower airway disease mortality were 1.068 (95% CI = 1.024, 1.113) and 1.029 (95% CI = 1.009, 1.050), respectively. In stratified analyses, exposures to PM₁₀ and NO₂ were associated with overall mortality in patients who were underweight and had a history of severe exacerbation.

Conclusion: In this large population-based study of patients with COPD, long-term PM₁₀ and NO₂ exposures were not associated with overall mortality but were associated with chronic lower airway disease mortality. PM₁₀ and NO₂ exposures were both associated with an increased risk of overall mortality, and with overall mortality in underweight individuals and those with a history of severe exacerbation.

Background: Afterload-related cardiac performance (ACP), a diagnostic parameter for septic cardiomyopathy, integrates both cardiac performance and vascular effects and could predict prognosis in septic shock.

Objectives: We hypothesized that ACP would also correlate with clinical outcomes in patients with chronic heart failure (HF).

Design: A retrospective study.

Methods: We retrospectively studied consecutive patients with chronic HF who underwent right heart catheterization and established an expected cardiac output-systemic vascular resistance (CO-SVR) curve model in chronic HF for the first time. ACP was calculated as CO_measured/CO_predicted × 100%. ACP > 80%, 60% < ACP ⩽ 80%, and ACP ⩽ 60% represented less impaired, mildly impaired, and severely impaired cardiovascular function, respectively. The primary outcome was all-cause mortality, and the secondary outcome was event-free survival.

Results: A total of 965 individual measurements from 290 eligible patients were used to establish the expected CO-SVR curve model (CO_predicted = 53.468 × SVR ^-0.799). Patients with ACP ⩽ 60% had higher serum NT-proBNP levels (P < 0.001), lower left ventricular ejection fraction (P = 0.001), and required dopamine more frequently (P < 0.001). Complete follow-up data were available in 263 of 290 patients (90.7%). After multivariate adjustment, ACP remained associated with both primary outcome (hazard ratio (HR) 0.956, 95% confidence interval (CI) 0.927-0.987) and secondary outcome (HR 0.977, 95% CI 0.963-0.992). Patients with ACP ⩽ 60% had the worst prognosis (all P < 0.001). ACP was significantly more discriminating (area under the curve of 0.770) than other conventional hemodynamic parameters in predicting mortality (Delong test, all P < 0.05).

Conclusion: ACP is a powerful independent hemodynamic predictor of mortality in patients with chronic HF. ACP and the novel CO-SVR two-dimensional graph could be useful in assessing cardiovascular function and making clinical decisions.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Chronic airway diseases (CAD), mainly asthma and chronic obstructive pulmonary disease (COPD), are frequently associated with different comorbidities. Among them, cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) pose problems for the simultaneous treatment of CAD and comorbidity. Indeed, there is evidence that some drugs used to treat CAD negatively affect comorbidity, and, conversely, some drugs used to treat comorbidity may aggravate CAD. However, there is also growing evidence of some beneficial effects of CAD drugs on comorbidities and, conversely, of the ability of some of those used to treat comorbidity to reduce the severity of lung disease. In this narrative review, we first describe the potential cardiovascular risks and benefits for patients using drugs to treat CAD and the potential lung risks and benefits for patients using drugs to treat CVD. Then, we illustrate the possible negative and positive effects on T2DM of drugs used to treat CAD and the potential negative and positive impact on CAD of drugs used to treat T2DM. The frequency with which CAD and CVD or T2DM are associated requires not only considering the effect that drugs used for one disease condition may have on the other but also providing an opportunity to develop therapies that simultaneously favorably impact both diseases.

Background: Sjögren's syndrome (SjS) is a rare autoimmune disease, and despite our knowledge of SjS, we still lack effective treatments. Chloroquine drugs used to treat autoimmune diseases are still the primary medicine for SjS but increase the risk of chloroquine retinopathy.

Objectives: The objective of this study is to use Optical Coherence Tomography Angiography (OCTA) images to monitor the microvascular changes in the fundus of SjS patients after hydroxychloroquine (HCQ) treatment and the feasibility of using them as diagnostic indicators.

Design: This is a retrospective observational cohort study.

Methods: Twelve healthy controls (HCs group; 24 eyes), 12 SjS patients (SjS group; 24 eyes), and 12 SjS patients treated with HCQ (HCQ group; 24 eyes) were recruited. Three-dimensional OCTA images of the retina were collected, and microvascular density was calculated for each eye. OCTA image segmentation for analysis was conducted using the central wheel division method (C1-C6), hemisphere segmentation method (SR, SL, IL, and IR), and the early treatment of diabetic retinopathy study method (ETDRS) (R, S, L, and I).

Results: Retinal microvascular density was significantly lower in the SjS patients compared to the HCs group (p < 0.05) and much lower in the HCQ group compared to the SjS patients (p < 0.05). The SjS and HCQ groups differed in the I, R, SR, IL, and IR regions in the superficial and deep retina and the S region in the superficial retina. The ROC curves of the relationship between the HCs and SjS groups and between the SjS and HCQ groups demonstrated good classification accuracy.

Conclusion: HCQ may contribute significantly to the microvascular alteration in SjS. Microvascular alteration is a potential marker with adjunctive diagnostic value. The MIR and the OCTA images of I, IR, and C1 regions showed high accuracy in minoring the alteration.

Background: Systemic lupus erythematosus-associated immune thrombocytopenia (SLE-ITP) is characterized by relapse. The risk factors of relapse and appropriate maintenance therapy strategy deserve further exploration.

Objectives: To determine the risk factors for relapse and appropriate maintenance therapy in significant SLE-ITP patients (a platelet count ⩽30 × 10⁹/l) after the first complete response.

Design: Retrospective cohort study using the medical records of 105 patients diagnosed as significant SLE-ITP in Fujian Medical University Union Hospital during December 2012 to March 2021. Patients were followed through a call for observations in January 2022.

Methods: Data including demographics, initial clinical feature, induction and maintenance therapy, and outcome at the end of follow-up were analyzed. Risk factors for significant relapse were analyzed using multivariate logistic regression models. The cumulative hazard of significant relapse and the duration of response were estimated, and the differences in outcome between groups were compared using the Cox regression analysis.

Results: A total of 65 significant SLE-ITP patients were eligible for the final analysis. Median [interquartile range (IQR)] follow-up duration and median [IQR] duration of response were 62.2 [41.0-79.6] months and 43.4 [20.3-68.7] months, respectively. After the first complete response, 19/65 (29.2%) had a significant relapse. Compared with sustained clinical remission (SCR) + sustained response (SR) group, significant relapse group had a higher proportion of discontinued patients (47.4% versus 8.7%, p = 0.001). Among the 13 discontinued patients, the duration of maintenance therapy of the patients in significant relapse group was significantly shorter than that of the patients in SCR + SR group (months, median [IQR], 43.1 [32.0-62.4] versus 12.0 [5.1-22.0], p = 0.009). Multivariate logistic regression analysis showed that drug withdrawal was an independent risk factor for significant relapse [odds ratio (OR) = 10.4, confidence interval (CI) 95% 2.2-47.8, p = 0.003]. There was no significant difference between glucocorticoids (GCs) + hydroxychloroquine (HCQ) group and GCs + HCQ + immunosuppressive agents (ISAs) group in significant relapse rate (26.7% versus 22.2%, p > 0.05). The two SR curves of GCs + HCQ and GCs + HCQ+ ISA group basically coincided by the Cox regression analysis, demonstrating comparable long-term outcomes (p > 0.05).

Conclusion: Drug withdrawal, especially abrupt withdrawal with insufficient duration of maintenance therapy, is an independent risk factor for significant relapse of SLE-ITP. HCQ combined with GCs is expected to be the first choice of the maintenance therapy for SLE-ITP patients.