Objective To synthesise evidence of the effectiveness of community based complex interventions, grouped according to their intervention components, to sustain independence for older people. Design Systematic review and network meta-analysis. Data sources Medline, Embase, CINAHL, PsycINFO, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to 9 August 2021 and reference lists of included studies. Eligibility criteria Randomised controlled trials or cluster randomised controlled trials with ≥24 weeks’ follow-up studying community based complex interventions for sustaining independence in older people (mean age ≥65 years) living at home, with usual care, placebo, or another complex intervention as comparators. Main outcomes Living at home, activities of daily living (personal/instrumental), care home placement, and service/economic outcomes at 12 months. Data synthesis Interventions were grouped according to a specifically developed typology. Random effects network meta-analysis estimated comparative effects; Cochrane’s revised tool (RoB 2) structured risk of bias assessment. Grading of recommendations assessment, development and evaluation (GRADE) network meta-analysis structured certainty assessment. Results The review included 129 studies (74 946 participants). Nineteen intervention components, including “multifactorial action from individualised care planning” (a process of multidomain assessment and management leading to tailored actions), were identified in 63 combinations. For living at home, compared with no intervention/placebo, evidence favoured multifactorial action from individualised care planning including medication review and regular follow-ups (routine review) (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty); multifactorial action from individualised care planning including medication review without regular follow-ups (2.55, 0.61 to 10.60; low certainty); combined cognitive training, medication review, nutritional support, and exercise (1.93, 0.79 to 4.77; low certainty); and combined activities of daily living training, nutritional support, and exercise (1.79, 0.67 to 4.76; low certainty). Risk screening or the addition of education and self-management strategies to multifactorial action from individualised care planning and routine review with medication review may reduce odds of living at home. For instrumental activities of daily living, evidence favoured multifactorial action from individualised care planning and routine review with medication review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living: combined activities of daily living training, aids, and exercise; and combined activities of daily living training, aids, education, exercise, and multifactorial action from individualised care planning and routine review with medication review and self-management strategies. For personal activities of daily living, evidence favoured combined exercise, multifactorial action from individualised care planning, and routine review with medication review and self-management strategies (0.16, −0.51 to 0.82; low certainty). For homecare recipients, evidence favoured addition of multifactorial action from individualised care planning and routine review with medication review (0.60, 0.32 to 0.88; low certainty). High risk of bias and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty. Conclusions The intervention most likely to sustain independence is individualised care planning including medicines optimisation and regular follow-up reviews resulting in multifactorial action. Homecare recipients may particularly benefit from this intervention. Unexpectedly, some combinations may reduce independence. Further research is needed to investigate which combinations of interventions work best for different participants and contexts. Registration PROSPERO CRD42019162195.

Objective: to investigate whether the association between blood pressure and clinical outcomes is different in older adults with and without frailty, using observational studies. Methods: MEDLINE, EMBASE and CINAHL were searched from 1st January 2000 to 13th June 2018. PROSPERO CRD42017081635. We included all observational studies reporting clinical outcomes in older adults with an average age over 65 years living in the community with and without treatment that measured blood pressure and frailty using validated methods. Two independent reviewers evaluated study quality and risk of bias using the ROBANS tool. We used generic inverse variance modelling to pool risks of all-cause mortality adjusted for age and sex. Results: nine observational studies involving 21,906 older adults were included, comparing all-cause mortality over a mean of six years. Fixed effects meta-analysis of six studies demonstrated that in people with frailty, there was no mortality difference associated with systolic blood pressure 140 mm Hg (HR 1.02, 95% CI 0.90 to 1.16). In the absence of frailty, systolic blood pressure 140 mm Hg (HR 0.86, 95% CI 0.77 to 0.96). Conclusions: evidence from observational studies demonstrates no mortality difference for older people with frailty whose systolic blood pressure is 140 mm Hg. Current evidence fails to capture the complexities of blood pressure measurement, and the association with non-fatal outcomes.

Frailty is a common condition in later life in which minor stressors may result in major changes in health. While the biological mechanisms of frailty are increasingly understood, relationships with the wider determinants of health, health inequalities and the concept of resilience are less well-established and the role of the clinician in their modification is less well understood.

Background National guidelines recommend trastuzumab for treatment of patients with metastatic HER2-positive gastric cancer (GC). There is currently no guideline indicating the number of biopsy specimens and the location from which they should be obtained to reliably determine the human epidermal growth factor receptor 2 (HER2) status in GC. The aim of this pilot study was (a) to quantify HER2-positive tumor cells in different tumor regions to assess the spatial heterogeneity of HER2 expression and (b) to establish the required number of biopsy specimens and the location from which they should be obtained within the tumor to achieve concordance between HER2 expression status in the biopsy specimens and the resection specimen. Methods HER2 expression was quantified in six different regions of 24 HER2-positive GC and in six virtual biopsy specimens from different luminal regions. Intratumoral regional heterogeneity and concordance between HER2 status in the biopsy specimens and the resection specimen were analyzed. Results HER2-positive cells were more frequent in the luminal tumor surface compared with deeper layers (p < 0.001). GCs with differentiated histological features were more commonly HER2 positive (p < 0.001). Assessment of HER2 expression status in five biopsy specimens was sufficient to achieve 100 % concordance between the biopsy specimens and the resection specimen. Conclusions This is the first study to suggest preferential HER2 positivity at the luminal surface in GC and to establish a minimum number of biopsy specimens needed to obtain a biopsy HER2 result which is identical to that from the whole tumor. Our study suggests that HER2 testing in five tumor-containing endoscopic biopsy specimens from the proximal (oral) part of the tumor is advisable. The results from this pilot study require validation in a prospective study.