Frailty as an Effect Modifier in Randomized Controlled Trials: A Systematic Review.

BACKGROUND: The effect of clinical interventions may vary by patients' frailty status. Understanding treatment effect heterogeneity by frailty could lead to frailty-guided treatment strategies and reduce overtreatment and undertreatment. This systematic review aimed to examine the effect modification by frailty in randomized controlled trials (RCTs) that evaluate pharmacological, non-pharmacological, and multicomponent interventions. METHODS: We searched PubMed, Web of Science, EMBASE, and ClinicalTrial.gov, from their inception to 8 December 2023. Two reviewers independently extracted trial data and examined the study quality with senior authors. RESULTS: Sixty-one RCTs that evaluated the interaction between frailty and treatment effects in older adults were included. Frailty was evaluated using different tools such as the deficit accumulation frailty index, frailty phenotype, and other methods. The effect of several pharmacological interventions (e.g., edoxaban, sacubitril/valsartan, prasugrel, and chemotherapy) varied according to the degree of frailty, whereas other treatments (e.g., antihypertensives, vaccinations, osteoporosis medications, and androgen medications) demonstrated consistent benefits across different frailty levels. Some non-pharmacological interventions had greater benefits in patients with higher (e.g., chair yoga, functional walking, physical rehabilitation, and higher dose exercise program) or lower (e.g., intensive lifestyle intervention, psychosocial intervention) levels of frailty, while others (e.g., resistance-type exercise training, moderate-intensive physical activity, walking and nutrition or walking) produced similar intervention effects. Specific combined interventions (e.g., hospital-based disease management programs) demonstrated inconsistent effects across different frailty levels. DISCUSSION: The efficacy of clinical interventions often varied by frailty levels, suggesting that frailty is an important factor to consider in recommending clinical interventions in older adults. REGISTRATION: PROSPERO registration number CRD42021283051.

Preference for primary care in Chinese homebound patients.

OBJECTIVE: This study aims to describe the preference for primary healthcare (PHC) and investigate associated factors among homebound residents in both rural and urban areas of China. It provides valuable insights to facilitate the rational allocation of healthcare resources and promote the utilization of PHC. METHODS: In this nationally representative cross-sectional study, we utilized the most recent data (2020) from the China Family Panel Studies (CFPS). Participants were recruited from 25 provincial-level administrative regions in both rural and urban areas of China. Homebound patients were asked to provide details about their individual characteristics, variables related to family caregiving, and preferences for PHC. Multivariable logistic models were used to analyze potential factors associated with preference for PHC. Estimates of association were reported as odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: The study found that 58.43% of rural patients reported a preference for PHC, while 42.78% of urban patients favored PHC. Compared to rural participants who did not received inpatient care in the past year, those who received inpatient care in the past year had 67% lower odds of choosing PHC (OR:0.33, 95% CI:0.19-0.59); Compared to rural participants who did not received family caregiving when ill, those who received family caregiving when ill had 59% lower odds of choosing PHC (OR: 0.41, 95% CI:0.21-0.77). Correspondingly, Compared to urban participants who did not received inpatient care in the past year, those who had received inpatient care in the past year had 75% lower odds of choosing PHC (OR: 0.25, 95% CI: 0.10-0.56); Compared to urban participants who did not received family caregiving when ill, those who received family caregiving when ill had 73% lower odds of choosing PHC (OR: 0.27, 95% CI: 0.11-0.63); Compared to urban participants who with agricultural Hukou, those with Non-agricultural Hukou had 61% lower odds of choosing PHC (OR: 0.39, 95% CI:0.18-0.83); Compared to urban participants living in the eastern part of mainland China, those living in the central part of China had 188% higher odds of choosing PHC (OR: 2.88, 95% CI: 1.14-7.29). CONCLUSION: Policymakers should focus on tailoring PHC to vulnerable populations and prioritizing family-based public health strategies for enhancing homebound patients' perceptions of PHC. Furthermore, further study is needed on whether the Hukou registration system affects the barriers that homebound patients experience in choosing healthcare providers.

Use of Primary Healthcare Among Chinese Older Adults With Functional Limitations.

The aim of this study was to assess the factors associated with primary healthcare (PHC) utilization among older adults with functional limitations, providing insights for improving the effectiveness of PHC for this population. We used the China Health and Retirement Longitudinal Study (CHARLS) dataset, which encompasses 28 provinces in China. Logistic regression was used to analyze the people-related, care context-related, and linkage-related factors associated with PHC utilization. Approximately 55.61% of older adults with functional limitations utilized PHC in the past month, regardless of visit frequency or extent. Participants with lower educational attainment, those reporting more pain, and those living in rural areas had a higher likelihood of PHC utilization. Participants who received inpatient care in the past year had a lower likelihood of PHC utilization. We recommend that policymakers complement existing PHC health programs with increased health and social welfare support for this population.

Use of home and community-based services and loneliness in older people with functional limitations: a cross-sectional study.

BACKGROUND: Loneliness is one of the major health problems among older adults. Among this population, home and community-based services (HCBS) have become increasingly popular. Despite its health benefits, little is known about the relationship between HCBS use and loneliness in older people with functional limitations. We aim to explore the characteristics of loneliness among older people with functional limitations and examine the association between HCBS use and loneliness in China. METHODS: We used a cross-sectional data from the 2018 China Health and Retirement Longitudinal Study, which includes a nationally representative sample of Chinese residents aged 65 and older with functional limitations. Logistic regression models were used to examine the associations between HCBS use and loneliness, and we further used propensity score matching to address potential sample selection bias. RESULT: In China, 46% of older people with functional limitations felt lonely and only 22% of older people with functional limitations reported using HCBS in 2018. Compared with participants who did not receive HCBS, those who received HCBS were less likely to report loneliness (OR = 0.81, 95% CI = 0.63, 0.99, p = 0.048), and the results remained significant after addressing sample selection bias using propensity score matching. CONCLUSION: Our results showed that loneliness was common among Chinese older people with functional limitations, and the proportion of HCBS use was low. There was robust evidence to support that among older people with functional limitations, HCBS use was associated with decreased loneliness. Further policies should promote the development of broader HCBS use for older people with functional limitations to reduce their loneliness.

Redesigning the patient classification system in China: A pilot study.

The current prototype patient classification system in China has not been updated for over six decades. In the present study, we adopted a hybrid patient classification method using both disease severity and activities of daily living scores to classify patients. The time motion approach was used to measure the direct nursing time of 551 general acute care patients. We found that patients in old Categories according to ability of self-care and disease severity 1-4 received approximately 7.1, 4.6, 3.4, and 4.5 h of direct nursing care, and the number of hours was not significantly different between Categories 2, 3, and 4. In contrast, patients in new Categories 1-4 received approximately 10.1, 6.9, 4.4, and 2.4 h of direct nursing care in 24 h. The nursing hours were significantly different between all pairings of the new categories. The new classification system can be used to make nursing care assignments and adjust staffing.

A SEER-Medicare analysis of the impact of metformin on overall survival in ovarian cancer.

OBJECTIVE: Determine whether metformin use is associated with improved survival in patients with ovarian, fallopian tube or primary peritoneal cancer. METHODS: All patients with a diagnosis of first epithelial ovarian cancer from 2007 to 2011 in the combined SEER-Medicare database were identified from the SEER registry primary site codes. Comorbidities, procedures and cancer treatment ICD-9 and HCPCS codes were used to search the Medicare claims files. Medication use was determined with National Drug Codes using the Medicare Part D event files. The primary outcome, overall survival, was assessed between metformin users and non-users using a Cox Proportional Hazards survival model. To control for confounding, metformin users were matched to non-metformin users using propensity scores. Effect of dosage on survival was assessed using discrete time survival analysis with pooled logistic regression (PLR). RESULTS: There were 2291 cases that met our inclusion criteria. Of these, 180 (7.9%) had been on metformin. The median age was 73years, with the majority of the population being White (83.5%) and treated with primary surgery (74.1%). Metformin use was not associated with overall survival in the entire cohort (HR 0.96, 95% CI 0.75-1.23) or in the matched sample cohort (HR 0.88, 95% CI 0.66-1.17). However, exploratory regression with time-varying coefficients suggests a protective metformin effect for women alive after 30months follow-up (HR=0.37, 95% 0.16-0.87). CONCLUSION: No statistically significant association was observed between metformin use and overall survival in a matched cohort of 360 ovarian cancer patients. However, exploratory modeling suggests metformin use may be protective in a certain subgroup of patients.

Distinguishing grade I meningioma from higher grade meningiomas without biopsy.

BACKGROUND: Many meningiomas are identified by imaging and followed, with an assumption that they are WHO Grade I tumors. The purpose of our investigation is to find clinical or imaging predictors of WHO Grade II/III tumors to distinguish them from Grade I meningiomas. METHODS: Patients with a pathologic diagnosis of meningioma from 2002-2009 were included if they had pre-operative MRI studies and pathology for review. A Neuro-Pathologist reviewed and classified all tumors by WHO 2007. All Brain MRI imaging was reviewed by a Neuro-radiologist. Pathology and Radiology reviews were blinded from each other and clinical course. Recursive partitioning was used to create predictive models for identifying meningioma grades. RESULTS: Factors significantly correlating with a diagnosis of WHO Grade II-III tumors in univariate analysis: prior CVA (p = 0.005), CABG (p = 0.010), paresis (p = 0.008), vascularity index = 4/4: (p = 0.009), convexity vs other (p = 0.014), metabolic syndrome (p = 0.025), non-skull base (p = 0.041) and non-postmenopausal female (p = 0.045). Recursive partitioning analysis identified four categories: 1. prior CVA, 2. vascular index (vi) = 4 (no CVA), 3. premenopausal or male, vi < 4, no CVA. 4. Postmenopausal, vi < 4, no CVA with corresponding rates of 73, 54, 35 and 10% of being Grade II-III meningiomas. CONCLUSIONS: Meningioma patients with prior CVA and those grade 4/4 vascularity are the most likely to have WHO Grade II-III tumors while post-menopausal women without these features are the most likely to have Grade I meningiomas. Further study of the associations of clinical and imaging factors with grade and clinical behavior are needed to better predict behavior of these tumors without biopsy.

Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival.

PURPOSE: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. METHODS AND MATERIALS: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. RESULTS: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. CONCLUSIONS: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.