Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial.

BACKGROUND: Older women experience more adverse drug reactions (ADRs) than older men. However, the underlying basis for this sex difference is unclear. Sex (biological status) and/or gender (sociocultural constructs) influences on patterns of inappropriate prescribing in multimorbid older adults may be one reason for this ADR sex difference. In this secondary analysis, we examined whether incident ADR sex differences could be related to concurrent sex differences in potentially inappropriate prescribing. DESIGN AND SETTING: A retrospective secondary analysis of sex differences in the prevalence of potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs), and ADRs among the 1537 participants (47.2% female, median [IQR] age 78 [72-84] years) was undertaken in the SENATOR clinical trial database, conducted in six large European medical centers. PARTICIPANTS AND METHODS: We looked specifically for male/female differences relating to PIMs and PPOs (defined by STOPP/START version 2 criteria) identified within 48 h of acute hospitalization. We also assessed sex differences for ADRs identified at 14 days from admission or discharge, whichever came first. ADRs were assessed by blinded endpoint adjudication panel consensus. RESULTS: During hospitalization, significantly more females experienced ≥1 ADR compared to males (28% and 21%, respectively; odds ratio 1.40, 95% CI 1.10-1.78, p < 0.005). Nine of the 11 STOPP-criteria PIMs showing a significant sex difference occurred more often in females. Of the four START-criteria PPOs showing a significant sex difference, all occurred more often in females. Some sex-associated PIMs reflect higher prevalence of related conditions in older women. CONCLUSION: We conclude that specific STOPP-criteria PIMs and START-criteria PPOs were identified more frequently in older women than older men during acute hospitalization, possibly contributing to higher ADR incidence in older women. Prescribers should appreciate sex differences in exposure to potentially inappropriate prescribing and ADR risk, given the preponderance of older women over older men in most clinical settings.

Guideline summary: assessment, diagnosis, care and support for people with dementia and their carers [Scottish Intercollegiate Guidelines Network SIGN Guideline 168].

The Scottish Intercollegiate Guidelines Network (SIGN) have recently published their guideline SIGN168 on 'Assessment, Diagnosis, Care, and Support for People with Dementia and their Carers'. The guideline makes evidence-based recommendations for best practice in the assessment, care and support of adults living with dementia. Topics featured in this guideline are limited to those prioritised by stakeholders, especially people with lived and living experience, and those not well covered under pre-existing guidance. We summarise the guideline recommendations related to identification and diagnosis of dementia, investigative procedures, postdiagnostic support living with dementia, including non-pharmacological approaches for distressed behaviours, using technology to support people with dementia, grief and dementia and changing needs of people with dementia. The guideline content is summarised as officially published, with additional commentary in the final section.

The Association of Dementia With Incident Adverse Drug Reactions in Hospitalized Older Adults.

BACKGROUND: Older adults with dementia commonly receive multiple medications and have higher hospitalization rates, elevating the risk of potentially inappropriate prescribing and in-hospital adverse drug reactions (ADRs). There is limited evidence examining ADRs in older adults with dementia during hospitalization. OBJECTIVES: Our aim was to assess the association between dementia and incidence of ADRs during hospitalization and to identify prevalent types of ADRs and medications linked to ADRs. DESIGN: Secondary analysis of the SENATOR trial database, which was a randomized controlled trial of an intervention to reduce ADRs in older inpatients with multimorbidity. SETTING AND PARTICIPANTS: A total of 1537 patients (47.2% females) with a mean age of 78.1 years were recruited from 6 European hospitals. METHODS: Sociodemographic data, functional status, cognitive status, clinical information, and ADR-related outcomes were extracted from the SENATOR database. Inpatients with dementia were identified based on prior International Classification of Diseases, Tenth Revision (ICD-10), dementia diagnosis, receiving acetylcholinesterase inhibitors or memantine, or a Mini-Mental State Examination score ≤24 at admission without concurrent delirium. RESULTS: Among participants, 392 (25.5%) were identified as having dementia. The proportion of patients with probable or certain incident in-hospital ADRs was similar between the groups with and without dementia (22.4% vs 25.4%, P > .05). However, in-hospital rates of probable or certain ADRs from 12 common categories were less frequently identified in patients with dementia compared to those without (19.4% vs 23%, P = .025). Major constipation (6.4% vs 9.9%, P = .03) and acute dyspepsia, nausea, or vomiting (2.8% vs 5%, P = .03) were less commonly observed ADRs in patients with dementia. CONCLUSIONS AND IMPLICATIONS: We did not observe an increased risk of in-hospital ADRs among inpatients with dementia. However, ADRs related to the gastrointestinal tract and identified by subjective symptoms were less frequently identified in this group. This study lays the groundwork for developing new tools for ADR diagnosis for older patients with dementia.

Enhancing Medication Safety through Implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in Ambulatory Older Adults.

INTRODUCTION: To promote optimal healthcare delivery, safeguarding older adults from the risks associated with inappropriate medication use is paramount. OBJECTIVE: This study aims to evaluate the effectiveness of implementing the Qatar Tool for Reducing Inappropriate Medication (QTRIM) in ambulatory older adults to enhance medication safety. METHOD: The QTRIM was developed by an expert consensus panel using the Beers Criteria and contained a list of potentially inappropriate medications (PIMs) based on the local formulary. Using quality improvement methodology, it was piloted and implemented in two outpatient pharmacy settings serving geriatric medicine and dermatology clinics at Rumailah Hospital, Qatar. Key performance indicators (KPIs) using implementation documentation as a process measure and the percentage reduction in PIM prescriptions as an outcome measure were assessed before and after QTRIM implementation. This study was conducted between July 2022 and September 2023. RESULTS: In the outpatient department (OPD) geriatric pharmacy, the prescription rate of PIMs was reduced from an average of 1.2 ± 0.7 PIMs per 1000 orders in 2022 to an average of 0.8 ± 0.2 PIMs per 1000 orders in 2023. In the OPD geriatric pharmacy, the results showed a 66.6% reduction in tricyclic antidepressants (TCAs) (from 30 to 10), a reduction in first-generation antihistamines by 51.7% (29 to 14), and muscle relaxants by 33.3% (36 to 24). While in dermatology, the older adult prescription rate of PIMs was reduced from an average of 8 ± 3 PIMs per 1000 orders in 2022 to a rate of 5 ± 3 PIMs per 1000 orders in 2023; the most PIM reductions were (49.4%) in antihistamines (from 89 to 45), while muscle relaxants and TCAs showed a minimal reduction. CONCLUSIONS: Implementing QTRIM with pharmacy documentation monitoring markedly reduced the PIMs dispensed from two specialized outpatient pharmacies serving older adults. It may be a promising effective strategy to enhance medication safety in outpatient pharmacy settings.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial.

PURPOSE: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay. METHODS: Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken. RESULTS: Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3 years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12 weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI. CONCLUSIONS: Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

BACKGROUND: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. METHODS: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. RESULTS: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. CONCLUSION: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.

Poor outcomes in patients with sepsis undergoing emergency laparotomy and laparoscopy are attenuated by faster time to care measures.

AIM: Emergency laparotomy and laparoscopy (EmLap) are amongst the commonest surgical procedures, with high prevalence of sepsis and hence poorer outcomes. However, whether time taken to receive care influences outcomes in patients requiring antibiotics for suspected infection remains largely unexplored. The aim of this work was to determine whether (1) time to care contributes to outcome differences between patients with and without suspected infection and (2) its impact on outcomes only amongst those with suspected infection. METHOD: Clinical information was retrospectively obtained from the 2017-2018 Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA). Time to care referred to six temporal variables describing radiological investigation, anaesthetic triage and surgical management. Outcome measures [mortality, readmission, hospital death, postoperative destination and length of stay (LoS)] were compared using adjusted and unadjusted regression analyses to determine whether the outcome differences could be explained by faster or slower time to care. RESULTS: Amongst 2243 EmLap patients [median age 65 years (interquartile range 51-75 years), 51.1% female], 892 (39.77%) received antibiotics for suspected infection. Although patients with suspected infection had faster time to care (all p ≤ 0.001) and worse outcomes compared with those who did not, outcome differences were not statistically significant when accounted for time (all p > 0.050). Amongst those who received antibiotics, faster time to care was also associated with decreased risk of postoperative intensive care unit (ICU) stay and shorter LoS (all p < 0.050). CONCLUSION: Worse outcomes associated with infection in EmLap patients were attenuated by faster time to care, which additionally reduced the LoS and ICU stay risk amongst those with suspected infection.

Clinical practice guidelines on the use of deep brain stimulation for the treatment of obsessive-compulsive disorder: systematic review.

BACKGROUND: Deep brain stimulation (DBS) has been proposed to improve symptoms of obsessive-compulsive disorder (OCD) but is not yet an established therapy. AIMS: To identify relevant guidelines and assess their recommendations for the use of DBS in OCD. METHOD: Medline, Embase, American Psychiatric Association PsycInfo and Scopus were searched, as were websites of relevant societies and guideline development organisations. The review was based on the PRISMA recommendations, and the search strategy was verified by a medical librarian. The protocol was developed and registered with PROSPERO (CRD42022353715). The guidelines were assessed for quality using the AGREE II instrument. RESULTS: Nine guidelines were identified. Three guidelines scored >80% on AGREE II. 'Scope and Purpose' and 'Editorial Independence' were the highest scoring domains, but 'Applicability' scores were low. Eight guidelines recommended that DBS is used after all other treatment options have failed to alleviate OCD symptoms. One guideline did not recommend DBS beyond a research setting. Only one guideline performed a cost-effectiveness analysis; the other eight did not provide details on safe or effective DBS protocols. CONCLUSION: Despite a very limited evidence base, eight of the nine identified guidelines supported the use of DBS for OCD as a last line of therapy; however, multiple aspects of DBS provision were not addressed.

Virus Infections in Older People.

Older people are more prone to viral infections, and often have worse outcomes. This was well demonstrated during the COVID-19 pandemic, where a disproportionate number of deaths occurred in the oldest and frailest people. The assessment of the older person with a viral infection is complicated by the high prevalence of multiple comorbidities and sensory or cognitive impairment. They often present with common geriatric syndromes such as falls or delirium, rather than the more typical features of a viral illness in younger people. Comprehensive geriatric assessment by a specialist multidisciplinary team is the gold standard of management, as viral illness is unlikely to present in isolation of other healthcare needs. We discuss the presentation, diagnosis, prevention, and management of common viral infections-respiratory syncytial virus, coronavirus, norovirus, influenza, hepatitis, herpes, and dengue viruses-with special consideration of infections in the older patient.

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. METHODS: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. RESULTS: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. CONCLUSIONS: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. CLINICAL TRIALS REGISTRATION: EudraCT, 2020-004123-16.

Does Estimated Glomerular Filtration Rate Predict In-Hospital Mortality in Acutely Unwell Hospitalized Oldest Old?

Globally the population of older adults is the fastest growing age group. Estimated glomerular filtration rate (eGFR) is an estimation of true kidney function with lower eGFR associated with higher mortality. However, few studies explore eGFR's prognostic value in the nonagenarian. We investigated the association between eGFR on admission and mortality among the nonagenarians hospitalised with acute illness. A retrospective analysis of a prospective cohort study included patients aged ≥ 90 admitted into three acute medical assessment units or acute geriatric wards in England and Scotland between November 2008 and January 2009. Association between eGFR and all-cause mortality was evaluated using the Cox proportional hazard models controlling for potential confounders including frailty. 392 patients with mean (SD) 93.0 ± 2.6 years (68.45% women) were included. The median (IQR) eGFR was 26.61 (18.41-40.41) mL/min/1.732. 63 died in in hospital. Low eGFR was not associated with mortality (Hazard ratio (HR) 1.00 (95% CI 0.98-1.02) overall or in sub-group analysis by frailty (HR 0.96 (0.92-1.01)) or by eGFR of ≤30 (HR 1.01 (0.95-1.06). We found no evidence of prognostic value of eGFR in predicting in-hospital mortality in the acutely unwell hospitalised nonagenarians.

Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis.

The following study aimed to systematically review and meta-analyse the literature on the relations between markers of nutritional status and long-term mortality, recurrence and all-cause hospital readmission following myocardial infarction (MI). Medline, EMBASE and Web of Science were searched for prospective cohort studies reporting the relationship between anthropometric and biochemical markers of nutritional status and nutritional assessment tools on long-term mortality, recurrence and all-cause hospital readmission in adult patients with an MI. Two reviewers conducted screening, data extraction and critical appraisal independently. Random-effects meta-analysis was performed. Twenty-seven studies were included in the qualitative synthesis and twenty-four in the meta-analysis. All eligible studies analysed BMI as their exposure of interest. Relative to normal weight, mortality was highest in underweight patients (adjusted Hazard Ratio (95% confidence interval): 1.42 (1.24-1.62)) and lower in both overweight (0.85 (0.76-0.94)) and obese patients (0.86 (0.81-0.91)), over a mean follow-up ranging from 6 months to 17 years. No statistically significant associations were identified between different BMI categories for the outcomes of recurrence and hospital readmission. Patients with low BMI carried a significant mortality risk post-MI; however due to the known limitations associated with BMI measurement, further evidence regarding the prognostic utility of other nutritional markers is required.

The relationship between nutritional status at the time of stroke on adverse outcomes: a systematic review and meta-analysis of prospective cohort studies.

CONTEXT AND OBJECTIVE: The impact of existing malnutrition on stroke outcomes is poorly recognised and treated. Evidence was systematically reviewed and quantified by meta-analysis. METHODS: MEDLINE, EMBASE and Web of Science were searched from inception to 11 January 2021 and updated in July. Prospective cohort studies, in English, evaluating anthropometric and biomarkers of nutrition on stroke outcomes were included. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network checklist. RESULTS: Twenty-six studies (n = 156 249) were eligible (follow-up: One month-14 years). Underweight patients had increased risk of long-term mortality (adjusted hazard ratio = 1.65,1.41-1.95), whilst overweight (0.80,0.74-0.86) and obese patients (0.80,0.75-0.85) had decreased risk compared to normal weight. Odds of mortality decreased in those with high serum albumin (odds ratio = 0.29,0.18-0.48) and increased with low serum albumin (odds ratio = 3.46,1.78-6.74) compared to normal serum albumin (30-35 g/L). Being malnourished compared to well-nourished, as assessed by the Subjective Global Assessment (SGA) or by a combination of anthropometric and biochemical markers increased all-cause mortality (odds ratio = 2.38,1.85-3.06) and poor functional status (adjusted odds ratio = 2.21,1.40-3.49). CONCLUSION: Nutritional status at the time of stroke predicts adverse stroke outcomes.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

Comparison of the clinical frailty score (CFS) to the National Emergency Laparotomy Audit (NELA) risk calculator in all patients undergoing emergency laparotomy.

AIM: There is evolving evidence that preoperative frailty predicts outcomes of older adults undergoing emergency laparotomy (EmLap). We assessed frailty scoring in an emergency surgical population that included patients of all ages and then compared this to an established perioperative prognostic score. METHOD: Data from the prospective Emergency Laparoscopic and Laparotomy Scottish Audit (ELLSA; November 2017-October 2018) was used. All adults over 18 were included. Frailty was measured using 7-point clinical frailty score (CFS). OUTCOME MEASURES: 30-day mortality, hospital length of stay (LOS), 30-day readmission. Areas under the receiver-operating characteristic (ROC) curves were calculated for CFS (1-7) and compared to the National Emergency Laparotomy Audit (NELA) score with Forest plots used to compare 30-day mortality across CFS and NELA categories. RESULTS: A total of 2246 patients (median age 65 years [IQR 51-75]; female 51%) underwent EmLap (60% for colorectal pathology). A total of 10.6% were frail preoperatively (≥CFS 5). As CFS increased so did 30-day mortality (2.1% CFS1 to 25.3% CFS6 and 7; ꭓ2 78.2, p < 0.001) and median LOS (10 days CFS1 to 20 days CFS6 and 7; p < 0.001). Readmission rates did not differ significantly across CFS. ROC (95% CI) for mortality was 0.71 (0.65-0.77) for CFS and 0.84 (0.78-0.89) for NELA. Addition of CFS to NELA did not increase ROC value. CONCLUSION: This study supports the prognostic role of frailty in the emergency surgical setting, finding increasing frailty to be associated with increased mortality and longer LOS in adults of all ages. Although NELA performed better, CFS remained predictive and has the advantage of being calculated preoperatively to aid decision-making and treatment planning.