Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Corrigendum: CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2024.1343124.].

CD4/CD8 ratio and CD8+ T-cell count as prognostic markers for non-AIDS mortality in people living with HIV. A systematic review and meta-analysis.

Background: In people living with HIV (PLHIV), the CD4/CD8 ratio has been proposed as a useful marker for non-AIDS events. However, its predictive ability on mortality over CD4 counts, and the role of CD8+ T-cell counts remain controversial. Methods: We conducted a systematic review and meta-analysis of published studies from 1996 to 2023, including PLHIV on antiretroviral treatment, and reporting CD4/CD8 ratio or CD8+ counts. The primary outcome was non-AIDS mortality or all-cause mortality. We performed a standard random-effects pairwise meta-analysis comparing low versus high CD4/CD8 ratio with a predefined cut-off point of 0.5. (CRD42020170931). Findings: We identified 2,479 studies for screening. 20 studies were included in the systematic review. Seven studies found an association between low CD4/CD8 ratio categories and increased mortality risk, with variable cut-off points between 0.4-1. Four studies were selected for meta-analysis, including 12,893 participants and 618 reported deaths. Patients with values of CD4/CD8 ratio below 0.5 showed a higher mortality risk (OR 3.65; 95% CI 3.04 - 4.35; I2 = 0.00%) compared to those with higher values. While the meta-analysis of CD8+ T-cell counts was not feasible due to methodological differences between studies, the systematic review suggests a negative prognostic impact of higher values (>1,138 to 1,500 cells/uL) in the long term. Conclusions: Our results support the use of the CD4/CD8 ratio as a prognostic marker in clinical practice, especially in patients with values below 0.5, but consensus criteria on ratio timing measurement, cut-off values, and time to event are needed in future studies to get more robust conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020170931, identifier CRD42020170931.

Treatments for alopecia areata: a network meta-analysis.

BACKGROUND: Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy. OBJECTIVES: To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults. SEARCH METHODS: The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA. DATA COLLECTION AND ANALYSIS: We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings. MAIN RESULTS: We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up. AUTHORS' CONCLUSIONS: We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.

Prognostic models for mortality after cardiac surgery in patients with infective endocarditis: a systematic review and aggregation of prediction models.

BACKGROUND: There are several prognostic models to estimate the risk of mortality after surgery for active infective endocarditis (IE). However, these models incorporate different predictors and their performance is uncertain. OBJECTIVE: We systematically reviewed and critically appraised all available prediction models of postoperative mortality in patients undergoing surgery for IE, and aggregated them into a meta-model. DATA SOURCES: We searched Medline and EMBASE databases from inception to June 2020. STUDY ELIGIBILITY CRITERIA: We included studies that developed or updated a prognostic model of postoperative mortality in patient with IE. METHODS: We assessed the risk of bias of the models using PROBAST (Prediction model Risk Of Bias ASsessment Tool) and we aggregated them into an aggregate meta-model based on stacked regressions and optimized it for a nationwide registry of IE patients. The meta-model performance was assessed using bootstrap validation methods and adjusted for optimism. RESULTS: We identified 11 prognostic models for postoperative mortality. Eight models had a high risk of bias. The meta-model included weighted predictors from the remaining three models (EndoSCORE, specific ES-I and specific ES-II), which were not rated as high risk of bias and provided full model equations. Additionally, two variables (age and infectious agent) that had been modelled differently across studies, were estimated based on the nationwide registry. The performance of the meta-model was better than the original three models, with the corresponding performance measures: C-statistics 0.79 (95% CI 0.76-0.82), calibration slope 0.98 (95% CI 0.86-1.13) and calibration-in-the-large -0.05 (95% CI -0.20 to 0.11). CONCLUSIONS: The meta-model outperformed published models and showed a robust predictive capacity for predicting the individualized risk of postoperative mortality in patients with IE. PROTOCOL REGISTRATION: PROSPERO (registration number CRD42020192602).

An International Consensus List of Potentially Clinically Significant Drug-Drug Interactions in Older People.

OBJECTIVES: We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. DESIGN: A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. SETTING AND PARTICIPANTS: Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. MEASURES: For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. RESULTS: Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. CONCLUSION AND IMPLICATIONS: We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies.

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

Fall-risk increasing drugs and recurrent injurious falls association in older patients after hip fracture: a cohort study protocol.

Polypharmacy and fall-risk increasing drugs (FRIDS) have been associated with injurious falls. However, no information is available about the association between FRIDS and injurious falls after hospital discharge due to hip fracture in a very old population. We aim to assess the association between the use of FRIDS at discharge and injurious falls in patients older than 80 years hospitalized due to a hip fracture. A retrospective cohort study using routinely collected health data will be conducted at the Orthogeriatric Unit of a teaching hospital. Patients will be included at hospital discharge (2014), with a 2-year follow-up. Fall-risk increasing drugs will be recorded at hospital discharge, and exposure to drugs will be estimated from usage records during the 2-year follow-up. Injurious falls are defined as falls that lead to any kind of health care (primary or specialized care, including emergency department visits and hospital admissions). A sample size of 193 participants was calculated, assuming that 40% of patients who receive any FRID at discharge, and 20% who do not, will experience an injurious fall during follow up. This protocol explains the study methods and the planned analysis. We expect to find a relevant association between FRIDS at hospital discharge and the incidence of injurious falls in this very old, high risk population. If confirmed, this would support the need for a careful pharmacotherapeutic review in patients discharged after a hip fracture. However, results should be carefully interpreted due to the risk of bias inherent to the study design.

Efficacy of non-pharmacological interventions to treat malnutrition in older persons: A systematic review and meta-analysis. The SENATOR project ONTOP series and MaNuEL knowledge hub project.

INTRODUCTION: We aimed to perform a review of SRs of non-pharmacological interventions in older patients with well-defined malnutrition using relevant outcomes agreed by a broad panel of experts. METHODS: PubMed, Cochrane, EMBASE, and CINHAL databases were searched for SRs. Primary studies from those SRs were included. Quality assessment was undertaken using Cochrane and GRADE criteria. RESULTS: Eighteen primary studies from seventeen SRs were included. Eleven RCTs compared oral nutritional supplementation (ONS) with usual care. No beneficial effects of ONS treatment, after performing two meta-analysis in body weight changes (six studies), mean difference: 0.59 (95%CI -0.08, 1.96) kg, and in body mass index changes (two studies), mean difference: 0.31 (95%CI -0.17, 0.79) kg/m2 were found. Neither in MNA scores, muscle strength, activities of daily living, timed Up&Go, quality of life and mortality. Results of other intervention studies (dietary counselling and ONS, ONS combined with exercise, nutrition delivery systems) were inconsistent. The overall quality of the evidence was very low due to risk of bias and small sample size. CONCLUSIONS: This review has highlighted the lack of high quality evidence to indicate which interventions are effective in treating malnutrition in older people. High quality research studies are urgently needed in this area.

Fall-risk increasing drugs and prevalence of polypharmacy in older patients discharged from an Orthogeriatric Unit after a hip fracture.

BACKGROUND: Polypharmacy and fall-risk increasing drugs (FRIDS) have been associated with injurious falls. We aimed to estimate the prevalence of polypharmacy and FRIDS in older patients discharged from an Orthogeriatric Unit after a hip fracture surgery. METHODS: This study describes the baseline findings of a 2-year retrospective cohort study. We included patients older than 80 years discharged from an Orthogeriatric Unit who were able to walk before surgery. Patient's baseline variables, total number of drugs, and FRIDS at hospital discharge were collected. RESULTS: We included 228 patients. The mean number of drugs and FRIDS prescribed at discharge was 11.6 ± 3.0 and 2.9 ± 1.6, respectively. Polypharmacy was prevalent in all patients except in three: 23.3% (5-9 drugs) and 75.9% (≥ 10 drugs). Only 11 patients had no FRIDS and 35.5% were on > 3 FRIDS. The most prevalent FRIDS were: agents acting on the renin-angiotensin system (43.9%) and anxiolytics (39.9%). The number of FRIDS was higher in patients with extreme polypharmacy (3.4 ± 1.5) than in those on 5-9 drugs (1.5 ± 1.0, p < 0.05). Independent people in performing instrumental activities had lower risk of extreme polypharmacy (≥ 10 drugs) or > 3 FRIDS: OR 0.39 (95% CI 0.18-0.83) and OR 0.41 (95% CI 0.20-0.84), respectively. People living in a nursing home had higher risk of > 3 FRIDS: OR 4.03 (95% CI 1.12-14.53). CONCLUSIONS: Polypharmacy and fall-risk increasing drugs are prevalent in patients discharged from orthogeriatric care after surgery for a hip fracture. Interventions on drug use at hospital discharge could have a potential impact on falls in this high-risk population.

Relevant outcomes for nutrition interventions to treat and prevent malnutrition in older people: a collaborative senator-ontop and manuel delphi study.

BACKGROUND AND AIMS: Research in malnutrition in older people is limited by the lack of consensus on relevant outcomes. Researchers of two European initiatives, the 'Malnutrition in the Elderly (MaNuEL) Knowledge Hub' (mostly experts in nutrition) and the Optimal Evidence-Based Non-drug Therapies in Older People (ONTOP) project (geriatricians) agreed to merge forces performing a systematic review of the effectiveness of nutritional interventions for the prevention and treatment of malnutrition in older persons. In a first step, we aimed to identify relevant outcomes for this review using a systematic approach and to explore if the rating of relevant outcomes differed depending on the researchers' professional background. METHODS: Following the ONTOP protocol, we searched all outcomes used in research of nutritional interventions for the prevention and treatment of malnutrition in older people. We carried out a web-based Delphi survey using a standardized list of 13 potentially relevant outcomes among 41 experts in geriatrics and nutrition who were asked to rate each outcome from 1 to 9 points: low importance (score 1-3), important but non-critical (score 4-6), and critical (score 7-9). Participants were informed that only those outcomes rated as critical (7-9 points) would be used in the literature review. After two rounds consultation, we compared the results from each group of experts: the ONTOP group formed by 13 geriatricians and the MaNuEL group formed by 28 experts in nutrition. Mean values were used for overall rating and the Mann-Whitney U test was used to see the differences on ratings between both groups. RESULTS: Mortality, morbidity, functional status, nutritional status and quality of life were considered critical outcomes by the whole group of experts. However, by analysing the ratings by the experts' professional background, geriatricians only rated mortality, morbidity and functional status as critical, while experts in nutrition (MaNuEL group) rated nutritional status, changes in dietary intake, compliance with the intervention, quality of life, and frailty status outcomes as critical too. Two outcomes, changes in dietary intake and compliance with the intervention, were rated with a significant different between the two professional groups (p < 0.05). CONCLUSIONS: Five outcomes were considered critical for research in nutritional interventions for the prevention and treatment of malnutrition in older persons: mortality, morbidity, functional status, nutritional status and quality of life by the whole panel of experts. However, more consensus is needed on the relevance of specific outcomes of nutritional interventions. Consensus processes within but also between relevant organizations are required to reach consensus and to contribute to this aim.

Nonpharmacological interventions to treat physical frailty and sarcopenia in older patients: a systematic overview - the SENATOR Project ONTOP Series.

BACKGROUND: Physical frailty (PF) and sarcopenia are predictors of negative health outcomes such as falls, disability, hospitalization, and death. Some systematic reviews (SRs) have been published on different nonpharmacological treatments of frailty and sarcopenia using heterogeneous definitions of them. OBJECTIVE: To critically appraise the evidence from SRs of the primary studies on nonpharmacological interventions to treat PF (defined by Fried's frailty phenotype) and sarcopenia (defined by the EWGSOP) in older patients. DESIGN: Overview of SRs and meta-analysis of comparative studies. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, EMBASE, and CINAHL were searched in October 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: SRs that included at least one comparative study evaluating any nonpharmacological intervention to treat PF or sarcopenia in older patients in any health care setting. Any primary study described in these SRs with experimental design was included. DATA EXTRACTION AND MANAGEMENT: Two reviewers independently screened titles, abstracts, and full-texts of articles. Quality assessment was carried out by using criteria from the Cochrane Collaboration and the GRADE working group. RESULTS: Ten SRs with 5 primary studies satisfied the inclusion criteria. The most frequent interventions in the included studies were physical exercise (4) and nutritional supplementation (2). Muscle strength (MS; except for one study in a frail population) and physical performance (PP; except for another study in a frail population) improved with exercise and amino acid supplementation in frail and sarcopenic old adults. Falls and activities of daily living were assessed in two studies with opposite results. The overall quality of the evidence was low. CONCLUSION: This overview of SRs highlights the importance of exercise interventions with or without nutritional supplementation to improve the PP in community-dwelling patients aged >65 years with PF and sarcopenia. MS improved with multidisciplinary treatment and exercise interventions in this population.

Nonpharmacologic Interventions to Prevent Pressure Ulcers in Older Patients: An Overview of Systematic Reviews (The Software ENgine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons [SENATOR] Definition of Optimal Evidence-Based Non-drug Therapies in Older People [ONTOP] Series).

BACKGROUND: Pressure ulcers (PUs) are frequent in older patients, and the healing process is usually challenging, therefore, prevention should be the first strategic line in PU management. Nonpharmacologic interventions may play a role in the prevention of PUs in older people, but most systematic reviews (SRs) have not addressed this specific population using convincing outcome measures. OBJECTIVE: To summarize and critically appraise the evidence from SRs of the primary studies on nonpharmacologic interventions to prevent PUs in older patients. DESIGN: SR and meta-analysis of comparative studies. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, EMBASE, and CINHAL (from inception to October 2013) were searched. A new search for updates in the Cochrane Database was launched in July 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: SRs that included at least 1 comparative study evaluating any nonpharmacologic intervention to prevent PUs in older patients, in any healthcare setting, were selected. Any primary study with experimental design was then identified and included. DATA EXTRACTION: From each primary study, quality assessment was undertaken as specified by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group. Interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis, using the incidence of new pressure ulcers as the main outcome measure. RESULTS: One hundred ten SRs with 65 primary studies satisfied the inclusion criteria. The most frequent interventions explored in these trials were support surfaces (41 studies), repositioning (8), and nutrition interventions (5). High quality of evidence was not found for any intervention, mainly because of a high risk of bias and imprecision. There is moderate quality evidence to support the use of alternating pressure support mattresses over usual hospital mattresses in medical and surgical inpatients, low quality evidence to support constant low pressure devices and Australian medical sheepskin over usual mattresses, and very low quality evidence to support nutrition interventions in hospital settings. No recommendations on hydration, repositioning, standardized risk assessment, or multicomponent interventions can be done. CONCLUSIONS: In older patients at high risk to suffer PUs, high-technology and low- technology support surfaces can significantly reduce the incidence of PUs. Nutrition intervention may also have a role in preventing PUs in hospital settings. More evidence is needed to support other recommendations, which is specially lacking for repositioning.