Current Medical Research and Opinion最新文献

Objective: We report patient-reported outcomes (PROs) measuring health-related quality of life (HRQoL) from the ROSEWOOD trial (NCT03332017), which demonstrated superior efficacy and a manageable safety profile with zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) in patients with heavily pretreated relapsed/refractory follicular lymphoma (R/R FL).

Methods: PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and EQ-5D-5L questionnaires at baseline and subsequently every 12 weeks. All QLQ-C30 domains and EQ-5D-5L visual analog scale (VAS) scores were analyzed descriptively. At the key clinical timepoints (weeks 12 and 24), a mixed model for repeated measures (MMRM) analysis was used to evaluate the key PRO endpoints, including global health status, physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting. Clinically meaningful change was defined as a ≥ 5-point mean difference from baseline and between the ZO and O arms.

Results: Patients were randomized to ZO (n = 145) or O (n = 72). By week 48, descriptive analysis results indicated that patients in the ZO arm demonstrated improved outcomes in role functioning and fatigue and nausea/vomiting symptoms, compared with those in the O arm. Both groups experienced improvements in pain symptoms. EQ-5D-5L VAS scores showed no observable differences between treatment arms through week 48. MMRM analysis revealed that the global health status/quality of life of patients treated with ZO improved, as did fatigue, at week 12. At week 24, patients in the ZO arm experienced a clinically meaningful improvement in role functioning, pain, and fatigue.

Conclusions: In patients with R/R FL, ZO was associated with improved PROs compared with O. These findings suggest that zanubrutinib contributed clinically meaningful benefits to patient HRQoL when added to obinutuzumab.

Trial registration: The ROSEWOOD trial is registered on ClinicalTrials.gov (BGB-3111-212; ClinicalTrials.gov identifier: NCT03332017).

Objective: Baricitinib is an oral, reversible and selective inhibitor of Janus kinase (JAK)1 and JAK2 that is approved as monotherapy or in combination with methotrexate for the treatment of adults with moderate-to-severe active rheumatoid arthritis (RA) who have responded inadequately to disease-modifying antirheumatic drugs. Evidence supporting the approved monotherapy indication is growing in real-world settings that reflect routine clinical practice.

Methods: Results of separate analyses of real-world data from the observational prospective RA-BE-REAL, Erlangen Baricitinib cohort, the BSRBR-RA, and Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registries, and the retrospective ORBIT-RA and SUSTAIN long-term chart reviews were reported, documenting baseline data and outcomes for a total of 932 patients with active RA receiving baricitinib as monotherapy. Findings were contrasted with those from a total of 850 patients receiving the drug as combination therapy. All analyses were descriptive and completed in September 2022.

Results: Across the patient registries and observational studies, 39.4%-69.6% of patients received baricitinib monotherapy for the treatment of active RA. In these patients, after about 6-12 months of treatment, 40.7%-93.8% and 55.6%-88.0% achieved remission or low disease activity according to the composite measures of disease activity 28-joint count and Clinical Disease Activity Index, respectively. Treatment continuation/discontinuation rates differed across the studies.

Conclusion: These findings suggest that baricitinib monotherapy can be a suitable treatment option in routine clinical practice for patients with RA, when used in accordance with current guidelines.

Background and aims: Orthostatic hypotension (Ohypo) and hypertension (Ohyper) have emerged early markers for high risk of cardiovascular events. Data on the prevalence and risk factors of Ohypo and Ohyper in patients with type 2 diabetes (T2D) are scarce.

Methods: Within the framework of the Brazilian Diabetes Study, this is an observational, cross-sectional study. The diagnosis of Ohypo was based on drops in systolic blood pressure (SBP) ≥20mmHg or diastolic blood pressure (DBP) ≥10mmHg when transitioning from sitting to standing. Ohyper was defined by either a SBP increase ≥20mmHg during this transition or a sustained elevation to 140 mmHg in otherwise normotensive individuals.

Results: The study population (n = 900) had a mean age of 57 ± 8 years, 57% male and the median T2D duration was 8 years. Sitting SBP and DBP were 140 ± 20 mmHg and 82 ± 11 mmHg, respectively. Of the total sample, 108 (12%) had Ohypo and 83 (9%) had Ohyper. Each 1-year increase in age was associated with 3.7% higher odds of orthostatic hypotension (OHypo). Additionally, each 1 mmHg increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) corresponded to a 3.0, 5.5, and 5.4% increase in the odds of OHypo, respectively. Ohyper risk did not associate with age but showed an inverse relationship with sitting BP values.

Conclusions: Ohypo and Ohyper are common occurrences in patients with T2D. Advanced age significantly elevates the risk of developing Ohypo, whereas sitting BP emerges as an independent risk factor for both Ohypo and Ohyper.

Objective: Tegoprazan represents a newly developed potassium-competitive acid blocker utilized for the treatment of acid-related disorders. The present study aimed to explore the therapeutic effectiveness of tegoprazan in Chinese individuals with duodenal ulcers (DU).

Methods: In the current multicenter, randomized, double-blind, double-dummy, parallel-group, non-inferiority, phase III clinical trial, individuals with DU underwent randomization 1:1 to be administered tegoprazan 50 mg or lansoprazole 30 mg once daily. The primary efficacy endpoint was the 6-week cumulative endoscopic ulcer healing rate. Secondary endpoints included 4-week endoscopic ulcer healing rate and relief of DU-related gastrointestinal symptoms at weeks 2, 4, and 6. Safety analysis encompassed adverse events (AEs) and laboratory indexes.

Results: The 6-week cumulative endoscopic ulcer healing rates were 96.9% (188/194) and 99.0% (189/191) in the tegoprazan and lansoprazole groups, respectively, indicating a difference of -2.0% (95% confidence interval (CI) = -4.9 to 0.8) in the full analysis set (FAS). The corresponding healing rates were 98.4% (185/188) and 99.5% (183/184) in the per-protocol set, respectively, indicating a difference of -1.1% (95% CI = -3.1 to 1.0). The 4-week healing rates in the tegoprazan and lansoprazole groups were 89.2% (173/194) and 88.5% (169/191) in the FAS, respectively, with a difference of 0.7% (95% CI = -5.6 to 7.0). Treatment-related AEs, all mild-to-moderate, were reported in 38.2% (78/204) and 48.2% (94/195) of participants in the tegoprazan and lansoprazole groups, respectively.

Conclusions: Tegoprazan 50 mg once daily is effective and non-inferior to lansoprazole 30 mg once daily in Chinese patients with DU, showing a promising safety and tolerability profile.

Clinicaltrials.gov registration number: NCT05010954.

Recent advances in development of amyloid-targeting therapies support the potential to slow the rate of progression of Alzheimer's disease. We conducted a narrative review of published evidence identified through a targeted search of the MEDLINE and EMBASE databases (2020-2023), recent presentations at disease-specific conferences, and data updates from cohort studies in Alzheimer's disease to describe the trajectory of the progression of Alzheimer's disease. Our findings enable the interpretation of clinical trial results and the value associated with slowing disease progression across outcomes of relevance to patients, care partners, clinicians, researchers and policymakers. Even at the earliest stages, Alzheimer's disease imposes a substantial burden on individuals, care partners, and healthcare systems. The magnitude of the burden increases with the rate of disease progression and symptom severity, as worsening cognitive decline and physical impairment result in loss of functional independence. Data from cohort studies also indicate that slowing disease progression is associated with decreased likelihood of needing extensive clinical care over at least 5 years, decreased care partner burden, and substantial individual and societal cost savings. Slowed disease progression is of significant benefit to individuals with Alzheimer's disease, their loved ones, and the healthcare system. As clinicians and policymakers devise strategies to improve access to treatment earlier in the disease spectrum, they should carefully weigh the benefits of slowing progression early in the disease (e.g. preservation of cognitive and functional abilities, as well as relative independence) to individuals, their loved ones, and broader society.

Background: Central Line Associated Blood Stream Infections (CLABSI) are significant complications for hospitalized patients. Several different approaches have been used to reduce CLABSI.

Objective: This study aimed to (1) describe a systematic approach used to analyze and reduce CLABSI rates in a surgical ICU (SICU) at a quaternary care medical facility (CLABSI reduction bundle) and (2) examine the association of the bundle on CLABSI rates in the SICU, compared to six unexposed health system ICUs.

Methods: Retrospective analysis of 14,022 adult patients with > 0 central line days within a single health system in the southeastern United States. The CLABSI intervention bundle was created and implemented in July 2021. Single and multiple interrupted time series analyses were performed to assess the impact of the CLABSI bundle on CLABSI rate in SICU (compared to control ICUs) pre- and post-intervention. Secondary analyses examined the association of the bundle with ICU mortality and length of stay.

Results: The CLABSI bundle was associated with a significant immediate effect in reducing the CLABSI rate in the SICU compared with control ICUs. There was no significant change in the slope of CLABSI rate post-intervention, compared to control ICUs. There was no significant association of the CLABSI reduction bundle on ICU length of stay or mortality in the SICU.

Conclusion: The CLABSI bundle was associated with an immediate reduction in CLABSI incidence in the SICU compared to unexposed ICUs. A simple, bundled intervention can be effective in reducing CLABSI incidence in a surgical ICU population.

Purpose: To investigate the incidence, risk factors, and clinical impact of persistent coronal imbalance (PCI) in Lenke5C adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF).

Methods: We analyzed the medical records of 112 Lenke5C AIS patients. They were grouped into PCI (+) group and PCI (-) group according to the occurrence of PCI at 2 years after surgery. Coronal and sagittal parameters were measured and compared between both groups preoperatively, immediately postoperatively, and 2 years postoperatively. Scoliosis Research Society-22 (SRS-22) score was used to evaluate clinical outcomes.

Results: Of the 112 patients, 12 had coronal imbalance persisting 2 years after surgery. Logistic regression analysis indicated risk factors including older age [odds ratio (OR) = 1.841, 95% confidence interval (CI) = 1.147-2.132, p = .001], lower preoperative flexibility main thoracic (MT) curve (OR = 1.308, 95% CI = 1.041-2.015, p = .016), greater preoperative apical vertebral translation (AVT) of the thoracolumbar/lumbar (TL/L) curve (AVT-TL/L) (OR = 2.291, 95% CI = 1.120-4.719, p = .001), larger preoperative lowest instrumented vertebra tilt (LIV lilt) (OR = 2.141, 95% CI = 1.491-3.651, p = .011), and postoperative immediate coronal imbalance (OR = 5.512, 95% CI = 4.531-6.891, p = .001). The satisfaction and total score of the SRS-22 scale in the PCI (+) group were lower than those in the PCI (-) group at 2 years after surgery (p <.05).

Conclusions: We found a 10.7% incidence of PCI in patients with Lenke5C AIS undergoing PSF. PCI adversely affects clinical outcomes. Risk factors of PCI included older age, reduced preoperative MT curve flexibility, increased preoperative AVT in the TL/L curve, greater preoperative LIV tilt, and immediate postoperative coronal imbalance.

Objective: This study investigated clinical characteristics, burden of uncontrolled seizures, and seizure-related healthcare resource utilization (HRU) among individuals living with drug-resistant focal epilepsy (FE) in the United States (US).

Methods: Medical charts of adults with drug-resistant FE who initiated third-line (3 L) anti-seizure medication were extracted from clinical practices in the US (1/1/2013-1/31/2020). The index date, defined as the date of 3 L initiation, was used to indicate the emergence of drug resistance. Individuals on cenobamate were followed for any length of time from the index date. Demographic and clinical characteristics were analyzed descriptively. Primary clinical outcomes included seizure burden (i.e. change in seizure frequency and time to the first and second seizure events) and epilepsy-related HRU.

Results: Overall, 189 neurologists/epileptologists contributed 345 charts of individuals living with drug-resistant FE (66% male; average age 24 years at diagnosis and 32 years at index date). 66% had ≥1 neurologic/neuropsychiatric comorbidity at baseline. Average monthly seizure rate decreased from 6.1 at baseline to 3.8 at follow-up; however, nearly half of individuals experienced worse/no change or only some improvement (<50% reduction) in seizure frequency. Most individuals (91%) had ≥1 epilepsy-related outpatient visit during follow-up. Unplanned HRU included emergency department visits (43%) and hospitalizations (24%), primarily due to breakthrough seizure events.

Conclusion: Despite the availability of many anti-seizure medications in the US, people living with drug-resistant FE continue to experience multiple seizures per month and incur substantial healthcare resources. Novel pharmacotherapies may help individuals living with drug-resistant epilepsy achieve seizure freedom.

Objective: To describe maternal demographics and compare clinical characteristics of infants with congenital cytomegalovirus (cCMV) identified through diagnostic codes and laboratory data in the United States during 2018-2023.

Methods: We used a CDC-licensed subset of HealthVerity data, which contained linked pregnant people-infant claims data from publicly and privately insured individuals during 2018-2023 (2023 Quarter 3 HealthVerity Maternal Outcomes Masterset data). We identified infants with cCMV using diagnostic codes or positive laboratory test results within 45 days of birth.

Results: Among 744 (4.6 per 10,000 live births) infants with cCMV during 2018-2023, 599 (81%) were identified by a diagnostic code only. Among 732 linked pregnant people, 91 (12%) had a diagnosis of CMV infection during pregnancy, with a similar distribution by age group and insurance type, but a lower proportion were Black as compared to those without CMV infection during pregnancy (14% vs. 29%, respectively). Overall, 452 (61%) infants had ≥1 cCMV-related clinical sign at birth and 185 (25%) had valganciclovir prescriptions. Eighty-eight (68%) infants identified by a positive laboratory test only had no cCMV-related signs and none had valganciclovir prescriptions.

Conclusions: Using healthcare claims data, we found a minimal overlap of cCMV identified by diagnostic codes and laboratory test results. A minority of linked pregnant people with infants with cCMV had a CMV diagnosis during pregnancy. cCMV surveillance will help better understand the validity of ICD codes to identify infants with cCMV, describe the spectrum of disease, and monitor the use of antivirals.