Prevalence and outcomes of frailty in unplanned hospital admissions: a systematic review and meta-analysis of hospital-wide and general (internal) medicine cohorts.

Background: Guidelines recommend routine frailty screening for all hospitalised older adults to inform care decisions, based mainly on studies in elective or speciality-specific settings. However, most hospital bed days are accounted for by acute non-elective admissions, in which the prevalence and prognostic value of frailty might differ, and uptake of screening is limited. We therefore did a systematic review and meta-analysis of frailty prevalence and outcomes in unplanned hospital admissions. Methods: We searched MEDLINE, EMBASE and CINAHL up to 31/01/2023 and included observational studies using validated frailty measures in adult hospital-wide or general medicine admissions. Summary data on the prevalence of frailty and associated outcomes, measurement tools, study setting (hospital-wide vs general medicine), and design (prospective vs retrospective) were extracted and risk of bias assessed (modified Joanna Briggs Institute checklists). Unadjusted relative risks (RR; moderate/severe frailty vs no/mild) for mortality (within one year), length of stay (LOS), discharge destination and readmission were calculated and pooled, where appropriate, using random-effects models. PROSPERO CRD42021235663. Findings: Among 45 cohorts (median/SD age = 80/5 years; n = 39,041,266 admissions, n = 22 measurement tools) moderate/severe frailty ranged from 14.3% to 79.6% overall (and in the 26 cohorts with low-moderate risk of bias) with considerable heterogeneity between studies (phet < 0.001) preventing pooling of results but with rates <25% in only 3 cohorts. Moderate/severe vs no/mild frailty was associated with increased mortality (n = 19 cohorts; RR range = 1.08-3.70), more consistently among cohorts using clinically administered tools (n = 11; RR range = 1.63-3.70; phet = 0.08; pooled RR = 2.53, 95% CI = 2.15-2.97) vs cohorts using (retrospective) administrative coding data (n = 8; RR range = 1.08-3.02; phet < 0.001). Clinically administered tools also predicted increasing mortality across the full range of frailty severity in each of the six cohorts that allowed ordinal analysis (all p < 0.05). Moderate/severe vs no/mild frailty was also associated with a LOS >8 days (RR range = 2.14-3.04; n = 6) and discharge to a location other than home (RR range = 1.97-2.82; n = 4) but was inconsistently related to 30-day readmission (RR range = 0.83-1.94; n = 12). Associations remained clinically significant after adjustment for age, sex and comorbidity where reported. Interpretation: Frailty is common in older patients with acute, non-elective hospital admission and remains predictive of mortality, LOS and discharge home with more severe frailty associated with greater risk, justifying more widespread implementation of screening using clinically administered tools. Funding: None.

Occupation and SARS-CoV-2 seroprevalence studies: a systematic review.

OBJECTIVE: To describe and synthesise studies of SARS-CoV-2 seroprevalence by occupation prior to the widespread vaccine roll-out. METHODS: We identified studies of occupational seroprevalence from a living systematic review (PROSPERO CRD42020183634). Electronic databases, grey literature and news media were searched for studies published during January-December 2020. Seroprevalence estimates and a free-text description of the occupation were extracted and classified according to the Standard Occupational Classification (SOC) 2010 system using a machine-learning algorithm. Due to heterogeneity, results were synthesised narratively. RESULTS: We identified 196 studies including 591 940 participants from 38 countries. Most studies (n=162; 83%) were conducted locally versus regionally or nationally. Sample sizes were generally small (median=220 participants per occupation) and 135 studies (69%) were at a high risk of bias. One or more estimates were available for 21/23 major SOC occupation groups, but over half of the estimates identified (n=359/600) were for healthcare-related occupations. 'Personal Care and Service Occupations' (median 22% (IQR 9-28%); n=14) had the highest median seroprevalence. CONCLUSIONS: Many seroprevalence studies covering a broad range of occupations were published in the first year of the pandemic. Results suggest considerable differences in seroprevalence between occupations, although few large, high-quality studies were done. Well-designed studies are required to improve our understanding of the occupational risk of SARS-CoV-2 and should be considered as an element of pandemic preparedness for future respiratory pathogens.

Limitations introduced by a low participation rate of SARS-CoV-2 seroprevalence data.

BACKGROUND: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate. METHODS: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021. RESULTS: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR. CONCLUSIONS: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

Global seroprevalence of SARS-CoV-2 antibodies: A systematic review and meta-analysis.

BACKGROUND: Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. METHODS: In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. RESULTS: We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. DISCUSSION: Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

Peritoneal macrophages are impaired in cathelicidin-deficient mice systemically challenged with Escherichia coli.

Cathelicidins are small, cationic peptides produced by macrophages with protective effects against infection although their involvement in phagocytosis is not fully understood. This study demonstrates that fewer macrophages were recruited in mice genetically deficient in cathelicidin (Camp-/-) during acute Escherichia coli-induced peritonitis and those macrophages had impaired phagocytosis. These defects seem due to endogenous functions of murine cathelicidin (CRAMP) as phagocytosis was not improved by synthetic human cathelicidin (LL-37) in a murine phagocytic cell line. This knowledge contributes to understanding the function of cathelicidins in the recruitment and function of phagocytic cells and differential roles between endogenous and exogenous cathelicidins.

Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review.

OBJECTIVE: Acutely painful osteoporotic vertebral compression fractures are associated with hospitalization and mortality in older adults. Calcitonin may be an alternative to opioid or nonopioid analgesia for treating acute compression fracture pain in emergency and primary care settings. This review summarizes pain, function, and adverse events associated with calcitonin. METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, clinical trials registries, and reference lists of included studies. Eligible studies evaluated the effect of synthetic calcitonins (salmon, eel, and human) on pain scores in adults ≥60 years old with a recent atraumatic compression fracture. Two reviewers screened studies, extracted data, and allocated bias in duplicate. A random effects meta-analysis evaluated standard mean difference (SMD) and heterogeneity (I2). RESULTS: Of 1,198 articles screened, 11 were included (9 in the meta-analysis). Treatment lasted from 14 days to 6 months. Pain was lower in the salmon calcitonin group (100-200 IU IM or NAS, daily) than the control group with high certainty of evidence at week 1 (SMD, -1.54; 95% confidence interval [CI], -2.02 - -1.06; I2 = 52%), representing a number needed to treat of two. The analgesic efficacy of salmon calcitonin at 4 weeks was unclear due to substantial heterogeneity. There was low certainty evidence that calcitonin did not increase the overall risk of adverse events, including nausea and vomiting (risk ratio, 2.10; 95% CI, 0.87-5.08; I2 = 47%). CONCLUSIONS: Calcitonin is beneficial and appears safe for treating acute pain associated with compression fractures. Further studies may improve the certainty of evidence.