Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVE: To systematically review the research conducted on prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries (LMICs) and to estimate the pooled prevalence of frailty and prefrailty in community-dwelling older adults in LMICs. DESIGN: Systematic review and meta-analysis. PROSPERO registration number is CRD42016036083. DATA SOURCES: MEDLINE, EMBASE, AMED, Web of Science, CINAHL and WHO Global Health Library were searched from their inception to 12 September 2017. SETTING: Low-income and middle-income countries. PARTICIPANTS: Community-dwelling older adults aged ≥60 years. RESULTS: We screened 7057 citations and 56 studies were included. Forty-seven and 42 studies were included in the frailty and prefrailty meta-analysis, respectively. The majority of studies were from upper middle-income countries. One study was available from low-income countries. The prevalence of frailty varied from 3.9% (China) to 51.4% (Cuba) and prevalence of prefrailty ranged from 13.4% (Tanzania) to 71.6% (Brazil). The pooled prevalence of frailty was 17.4% (95% CI 14.4% to 20.7%, I²=99.2%) and prefrailty was 49.3% (95% CI 46.4% to 52.2%, I²=97.5%). The wide variation in prevalence rates across studies was largely explained by differences in frailty assessment method and the geographic region. These findings are for the studies with a minimum recruitment age 60, 65 and 70 years. CONCLUSION: The prevalence of frailty and prefrailty appears higher in community-dwelling older adults in upper middle-income countries compared with high-income countries, which has important implications for healthcare planning. There is limited evidence on frailty prevalence in lower middle-income and low-income countries

Association between frailty and disability among rural community-dwelling older adults in Sri Lanka: a cross-sectional study

OBJECTIVE: We examined the association between frailty and disability in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 746 community-dwelling adults aged ≥60 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Frailty was assessed using the Fried phenotype. Disability was operationalised in terms of having one or more activity limitation/s in instrumental activities of daily living (IADL) and basic activities of daily living (BADL). RESULTS: The median age of the sample was (median 68; IQR 64-75) years and 56.7% were female. 15.2% were frail and 48.5% were prefrail. The prevalence of ≥1 IADL limitations was high, 84.4% among frail adults. 38.7% of frail adults reported ≥1 BADL limitations. Over half of frail older adults (58.3%) reported both ≥1 physical and cognitive IADL limitations. Being frail decreased the odds of having no IADL limitations, and was associated with a higher count of IADL limitations. No significant association was found between prefrailty and number of IADL limitations. CONCLUSIONS: The prevalence of ≥1 IADL limitations was high among rural community-dwelling frail older adults. Findings imply the greater support and care required for rural Sri Lankan frail older adults to live independently in the community

Prevalence of frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka: a population-based cross-sectional study

OBJECTIVE: Our main objective was to describe the prevalence and associated sociodemographic factors of frailty and pre-frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: Community-based cross-sectional study. SETTING: The study was conducted in rural areas of Kegalle district in Sri Lanka. PARTICIPANTS: A total of 746 community-dwelling older adults aged ≥60 years were included in the study. RESULTS: The prevalence of frailty and pre-frailty in rural Kegalle district was 15.2% (95% CI 12.3% to 18.6%) and 48.5% (95% CI 43.8% to 53.2%), respectively. We found a strong association between age and both frailty and pre-frailty. There were strong associations between longest-held occupation and frailty and education level and pre-frailty. CONCLUSIONS: The prevalence of frailty in this rural Sri Lankan older population was high compared with high-income and upper middle-income countries. The profile of health and social care services in Sri Lanka needs to address frailty and its consequences

High systemic IL-6 is associated with worse prognosis in patients with non-small cell lung cancer

Characteristic cytokine patterns have been described in different cancer patients and they are related to their diagnosis, prognosis, prediction of treatment responses and survival. A panel of cytokines was evaluated in the plasma of non-small cell lung cancer (NSCLC) patients and healthy controls to investigate their profile and relationship with clinical characteristics and overall survival. The case-controlled cross-sectional study design recruited 77 patients with confirmed diagnosis of NSCLC (cases) and 91 healthy subjects (controls) aimed to examine peripheral pro-inflammatory and anti-inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF and IFN-gamma) by Cytometry Beads Arrays (CBA Flex) in. The cytokine IL-6 showed a statistically significant difference among groups with increased expression in the case group (p < 0.001). The correlation between the cytokines expression with patient's clinical characteristics variables revealed the cytokine IL-6 was found to be associated with gender, showing higher levels in male (p = 0.036), whereas IL-17A levels were associated with TNM stage, being higher in III-IV stages (p = 0.044). We observed worse overall survival for individuals with high levels of IL-6 when compared to those with low levels of this cytokine in 6, 12 and 24 months. Further studies of IL-6 levels in independent cohort could clarify the real role of IL-6 as an independent marker of prognostic of NSCLC.Conselho Nacional de Desenvolvimento Científico e Tencnológico (CNPq) [Grant number 401775/2012-7 to ALF]; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [Grant number 2014/ 23414-8 to EMS]info:eu-repo/semantics/publishedVersio

Direct Identification of the Meloidogyne incognita Secretome Reveals Proteins with Host Cell Reprogramming Potential

The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin) that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins). Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth). Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals

(Homo)glutathione Deficiency Impairs Root-knot Nematode Development in Medicago truncatula

Root-knot nematodes (RKN) are obligatory plant parasitic worms that establish and maintain an intimate relationship with their host plants. During a compatible interaction, RKN induce the redifferentiation of root cells into multinucleate and hypertrophied giant cells essential for nematode growth and reproduction. These metabolically active feeding cells constitute the exclusive source of nutrients for the nematode. Detailed analysis of glutathione (GSH) and homoglutathione (hGSH) metabolism demonstrated the importance of these compounds for the success of nematode infection in Medicago truncatula. We reported quantification of GSH and hGSH and gene expression analysis showing that (h)GSH metabolism in neoformed gall organs differs from that in uninfected roots. Depletion of (h)GSH content impaired nematode egg mass formation and modified the sex ratio. In addition, gene expression and metabolomic analyses showed a substantial modification of starch and γ-aminobutyrate metabolism and of malate and glucose content in (h)GSH-depleted galls. Interestingly, these modifications did not occur in (h)GSH-depleted roots. These various results suggest that (h)GSH have a key role in the regulation of giant cell metabolism. The discovery of these specific plant regulatory elements could lead to the development of new pest management strategies against nematodes

Perspective on oncogenic processes at the end of the beginning of cancer genomics

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The association between frailty and quality of life among rural community-dwelling older adults in Kegalle district of Sri Lanka: a cross-sectional study

PURPOSE: The objective of this study was to estimate the cross-sectional association of frailty status with overall and domain-specific quality of life (QoL) in rural community-dwelling older adults in Kegalle district of Sri Lanka. METHODS: A population-based cross-sectional study was conducted with 746 community-dwelling older adults aged ≥ 60 years living in the rural areas of Kegalle district of Sri Lanka in 2016. A three-stage probability sampling design was used to recruit participants. Frailty and QoL were assessed using the Fried phenotype and Older People's Quality of Life Questionnaire, respectively. Multivariable linear regression was used to estimate the association of frailty with QoL after accounting for the complex sampling design. RESULTS: The median (IQR) age of the sample was 68 (64:75) years and comprised of 56.7% women. 15.2% (95% CI 12.4%, 18.7%) were frail and 48.5% (95% CI 43.9%, 53.2%) were pre-frail. The unadjusted means (SE) of the total QoL score for the robust, pre-frail and frail groups were 139.2 (0.64), 131.8 (1.04) and 119.2 (1.35), respectively. After adjusting for covariates in the final multivariable model, the estimated differences in mean QoL were lower for both frail and pre-frail groups versus robust. The estimated reduction in the total QoL score was 7.3% for those frail and 2.1% for those pre-frail. All QoL domains apart from 'social relationships and participation', 'home and neighbourhood' and 'financial circumstances' were associated with frailty. CONCLUSIONS: Frailty was associated with a small but significant lower quality of life in this rural Sri Lankan population, which appears largely explained by 'health' and 'independence, control over life and freedom' QoL domains. Interventions aiming to improve quality of life in frail older adults should consider targeting these aspects