Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

INTRODUCTION: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. METHODS: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. RESULTS: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). CONCLUSION: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

A descriptive analysis of drug-drug interactions and corresponding adverse drug reactions in multimorbid older inpatients: findings from the SENATOR trial.

PURPOSE: Drug-drug interactions (DDIs) are prevalent among multimorbid and polymedicated older adults and can increase the risk of adverse drug reactions (ADRs), hospital admissions, and mortality. This study describes the incidence and prevalence of 66 clinically relevant DDIs and analyses the occurrence of 12 corresponding predefined ADRs in older inpatients enrolled in the SENATOR trial. METHODS: The sub-study of the SENATOR trial that involved 1537 multimorbid older inpatients, recruited from 2016 to 2018 in six academic teaching hospitals in Belgium, Iceland, Ireland, Italy, Scotland, and Spain respectively, and analysed 66 potentially clinically significant DDIs. Descriptive analysis determined DDI and corresponding ADR prevalence/incidence. RESULTS: At baseline (median age: 78 [72, 84], 52.8% male), the prevalence of patients with DDIs was high (50.9%), increased during hospitalisation (55.2%) and reduced to 49.7% after 12 weeks. The most common DDIs were: ≥ 2 potassium reducing drugs (17.1%), ≥ 3 centrally acting drugs (9.0%), and SSRI + loop/thiazide diuretic (7.2%). Of all participants, one-third experienced a prevalent (36.6%)/incident (35.8%) ADR. Major serum electrolyte disturbance had the highest incidence (10.7%)/prevalence (11.5%). Incident ADRs were more common in patients with DDIs (p = 0.013). A higher prevalence of new onset falls (p = 0.013), major constipation (p = 0.004), and major serum electrolyte disturbances (p = 0.006) was observed in patients with related and thus potentially causal DDIs. CONCLUSIONS: Clinicians should, be aware of DDIs and the involved drug classes that can lead to an increased rate of ADRs in older multimorbid inpatients. Regularly reevaluating the appropriateness of the frequently prescribed drug classes and initiating judicious deprescribing is recommended.

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.

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.

Anticholinergic burden and health-related quality of life among adult patients in a resource-limited setting: a cross-sectional study.

BACKGROUND: Anticholinergic medications are now widely acknowledged for their unfavorable risk-to-benefit profile owing to their adverse effects. Health-related quality of life (HRQoL) is commonly regarded as a crucial person-centered outcome. AIM: This study aimed to investigate the association between anticholinergic burden and HRQoL in hospitalized and ambulatory patients seen in Ethiopia. METHOD: This cross-sectional study utilized a questionnaire and medical records to collect data from a convenience sample of adult patients attending both inpatient wards and ambulatory clinic of University of Gondar Comprehensive Specialized Hospital between April and September 2022. Anticholinergic burden was measured by anticholinergic cognitive burdens scale (ACBS), while HRQoL was measured using EQ5D-index (Euroqol-5 dimensions-5-Levels index) and EQ5D-VAS (visual analogue scale). Linear regression was used to assess the influence of high anticholinergic burden (ACBS score ≥ 3) on EQ5D-index and EQ5D-VAS, with adjustments made for sociodemographic and clinical confounders. RESULTS: A total of 828 patients participated in this study (median (IQR) age was 45.0 (30, 60) and 55.9% were female). On multiple linear regression analysis, high anticholinergic burden was associated with a statistically significant decline in HRQoL, as evidenced by reductions in both EQ5D index (- 0.174 (- 0.250, - 0.098)) and EQ5D-VAS scores (- 9.4 (- 13.3, - 5.2)). CONCLUSION: A significant association between high anticholinergic burden and diminished HRQoL was found among a relatively younger cohort in a resource-limited setting, even after adjustment for important confounding variables. Clinicians should be cognizant of the cumulative impact of anticholinergic burden on HRQoL outcomes and strive to minimize anticholinergic burden.

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.

Anticholinergic burden among in-patients: a cross-sectional study on prevalence, determinants, and impact on mortality in Ethiopia.

Background: Numerous studies report that anticholinergic burden (ACB) has been linked with several health consequences, including increased hospital admissions, prolonged hospitalization, and physical and cognitive impairment. However, low- and middle-income settings, as well as younger individuals, are underrepresented. Objectives: To assess the prevalence and determinants of ACB, and to assess the impact of ACB on in-hospital mortality among adult in-patients at University of Gondar Comprehensive Specialized Hospital (UOGCSH). Design: A cross-sectional study was conducted from June to August 2022 at UOGCSH among adult in-patients. Methods: A pre-tested questionnaire was utilized to collect data from patients and their corresponding medical charts. A consecutive sampling technique was used to select the participants. Descriptive statistics were used to summarize socio-demographic and clinical characteristics. Chi-squared, Fisher's exact, and Wilcoxon rank sum tests, as appropriate, were used to determine associations between independent variables and ACB. Kaplan-Meier survival curve and Cox proportional hazards regression test were used to assess the impact of ACB on in-hospital mortality. Results: A total of 420 adult in-patients, median (interquartile range) age of 38 (26, 55) years, participated in this study. Over half (58.3%) were exposed to anticholinergic medicines, with a high ACB (⩾3) seen in 11.2% of participants. High ACB was associated with higher median number of medicines per patient (p = 0.003) higher median hospital length of stay (p = 0.033), and having mental and behavioral disorders (p < 0.001). No significant association was found between ACB and in-hospital mortality (log-rank test p = 0.26, Cox regression adjusted hazard ratio: 1.47, 95% CI: 0.335-6.453, p = 0.61). Conclusion: Among adult in-patients, a significant majority (58.3%) were subjected to medications possessing anticholinergic properties, with a noteworthy 11.2% of the study subjects exhibiting a high ACB. Participants with higher median length of hospital stay were more likely to have high ACB even in this relatively younger adult patient population.

Background: Anticholinergics refers to substances that block the action of the neurotransmitter acetylcholine in the body. Previous studies have shown that medicines exhibiting anticholinergic effects could lead to increased hospital admissions, longer hospital stays, and both physical and cognitive impairments. Objective: In this study, we aimed to assess how medicines exhibiting anticholinergic effects might affect patients in Ethiopian in-patient settings. Methods: We conducted a cross-sectional study from June to August 2022, collecting data from adult in-patients through a questionnaire and medical charts. We used a widely recognized tool called Anticholinergic Cognitive Burden Score to measure anticholinergic burden. We used statistical analyses to identify associations between the use of anticholinergic medicines and various factors, including the number of medicines per patient and the length of hospital stay. Additionally, we explored the impact of anticholinergic burden on in-hospital mortality. Results: Out of the 420 participants, 245 were exposed to medicines with anticholinergic properties. High anticholinergic burden was observed in 47 patients. Patients with mental and behavioral disorders were more likely to have high anticholinergic burden, while those with diseases of the digestive system were less likely. Moreover, a high anticholinergic burden was linked to a greater median number of medicines per patient and an extended median hospital length of stay. However, the study found no significant difference in in-hospital mortality between patients with high and low anticholinergic burden. Conclusion: The study highlights that a significant proportion of the participants were exposed to medicines with anticholinergic properties, and a notable percentage experienced a high anticholinergic burden. This burden was particularly associated with mental and behavioral disorders, the use of higher number of medicines, and longer hospital stay. Importantly, the research did not find a clear link between anticholinergic burden and in-hospital mortality after accounting for other factors.

Understanding the impact of medicines with anticholinergic properties on patients at University of Gondar Hospital.

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.

Classifying the non-metabolic demands of different physical activity types: The Physical Activity Demand (PAD) typology.

Different physical activity types vary in metabolic demand (intensity), but also in non-metabolic physical demand (balance, co-ordination, speed and flexibility), cognitive demand (attention, memory and decision making), and social demand (social interaction). Activity types with different combinations of demands may have different effects on health outcomes but this cannot be formally tested until such demands can be reliably quantified. The present Delphi expert consensus study aimed to objectively quantify the cognitive, physical and social demands of different core physical activity types and use these scores to create a formal Physical Activity Demand (PAD) typology. International experts (n = 40; experts in cognitive science, psychology, sports science and physiology; 7 different nationalities; 18 male/22 female; M = 13.75 years of disciplinary experience) systematically rated the intrinsic cognitive, physical and social demands of 61 common activity types over 2-rounds of a modified Delphi (expert consensus) study. Consensus (>70% agreement) was reached after 2 rounds on the demands of 59/61 activity types. Cognitive, physical and social demand scores were combined to create an overall non-metabolic demand rating for each activity type, and two-step cluster-analysis was used to identify groups of activities with comparable demand profiles. Three distinct clusters of activities were identified representing activity types with low (n = 12 activities; e.g. domestic cleaning), moderate (n = 23 activities; e.g. tai-chi) and high (n = 24 activities; e.g. football) total non-metabolic demands. These activity types were then organised into a formal typology. This typology can now be used to test hypotheses about if and why physical activity types with different combinations of cognitive, physical and social demands affect health outcomes in different ways.

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.