Barriers and facilitators to deprescribing of cardiovascular medications: a systematic review.

OBJECTIVE To synthesise the current knowledge on barriers and facilitators to deprescribing cardiovascular medications (CVMs) at the levels of patients, informal caregivers and healthcare providers (HCPs). DESIGN/SETTING We conducted a systematic review of studies exploring/assessing patient, informal caregiver and/or HCP barriers and/or facilitators to deprescribing CVMs. DATA SOURCES Ovid/MEDLINE and Embase from January 2003 to November 2021. DATA EXTRACTION AND SYNTHESIS We performed a deductive thematic analysis based on the framework of specific barriers and facilitators to deprescribing CVMs created by Goyal et al. We added a quantification of the occurrence of categories and themes in the selected articles to identify the resounding themes that indicate the greater impetus to address in future research. RESULTS Most frequent deprescribing barriers for patients, informal caregivers and HCPs included uncertainty due to lack of evidence regarding CVM deprescribing (in n=10 studies), fear of negative consequences following deprescribing (n=13) and social influences (n=14). A frequently reported facilitator to deprescribing, especially for patients and informal caregivers, was the occurrence of adverse drug events (n=7). Another frequently reported facilitator for patients were dislike of CVMs (n=9). Necessity and benefit of CVMs were seen as barriers or facilitators similarly by patients and HCPs. CONCLUSION The differences in patient, informal caregiver and HCP regarding barriers and facilitators to deprescribing CVMs stress the need for ground discussions about beliefs and preferences of each stakeholder implicated in deprescribing decisions. Furthermore, HCP uncertainty regarding CVM deprescribing highlights the need to provide HCPs with tools that enable sharing the risks and benefits of deprescribing with patients and ensure a safe deprescribing process. PROSPERO REGISTRATION NUMBER CRD42020221973

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

AIMS/HYPOTHESIS Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. METHODS 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA. RESULTS In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (β = -0.26, p = 0.045) after integrating effects of height (β = -0.38, p = 0.01), insulin treatment (β = 0.42, p = 0.002), retinopathy treated by laser (β = 0.26, p = 0.02), and total cholesterol levels (β = 0.3, p = 0.03) by multivariable analysis. CONCLUSIONS The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

BACKGROUND Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016

Mussel as a Tool to Define Continental Watershed Quality

Bivalves appear as relevant sentinel species in aquatic ecotoxicology and water quality assessment. This is particularly true in marine ecosystems. In fact, several biomonitoring frameworks in the world used mollusks since several decades on the base of contaminant accumulation (Mussel Watch, ROCCH) and/or biological responses called biomarker (OSPAR) measurements. In freshwater systems, zebra and quagga mussels could represent alternative sentinels, which could be seen as the counterparts of mussel marine species. This chapter presents original studies and projects underlying the interest of these freshwater mussels for water quality monitoring based on contaminant accumulation and biomarker development measurements. These sentinel species could be used as a tool for chemical/biological monitoring of biota under the European water framework directive and for the development of effect-based monitoring tools

Lung transplantation after allogeneic stem cell transplantation : a pan-European experience

Late-onset noninfectious pulmonary complications (LONIPCs) affect 6% of allogeneic stem cell transplantation (SCT) recipients within 5 years, conferring subsequent 5-year survival of 50%. Lung transplantation is rarely performed in this setting due to concomitant extrapulmonary morbidity, excessive immunosuppression and concerns about recurring malignancy being considered contraindications. This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan-Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients proved comparable to controls (p=0.75). Sepsis accounted for 15 out of 37 deaths (41%), with prior mechanical ventilation (HR 6.9, 95% CI 1.0-46.7; p Lung transplantation outcomes following SCT were comparable to other end-stage diseases. Lung transplantation should be considered feasible in selected candidates. No SCT-specific factors influencing outcome were identified within this carefully selected patient cohort.Peer reviewe

Early Sasanian landscape modification: New geoarchaeological evidence from the Ardashir Pond in southwest Iran (Palace of Ardashir, third century CE)

The Sasanian period (224–651 CE) marked an era of large‐scale urban projects insouthwest Asia, including Iran's semi‐arid highlands, with particular efforts to ma-nipulate water bodies. This study presents a recent interdisciplinary investigation ofa spring‐fed pond at the entrance of the Palace of Ardashir (Firuzabad plain,southwest Iran), part of a recently registered World Heritage site. Historical ac-counts suggest that the entire water system of the plain, including the pond, un-derwent a hydraulic re‐organization at the beginning of the Sasanian period, a factthat has never been investigated geoarchaeologically. A series of sediment coreswere retrieved from the pond to probe its evolution and examine the extent of itslandscape modification. The cores were sedimentologically described andradiocarbon‐dated with age–depth models established based on 57 AMS (accel-erator mass spectrometry)14C dates to understand the basin's depositional history.The results indicate that (i) Ardashir Pond has existed as part of a larger wetlandcomplex since at least 4500 years ago, (ii) it was substantially enlarged at the be-ginning of the Sasanian era, and (iii) it was abandoned at the end of the Sasanianperiod. The Ardashir Pond is one of the first geoarchaeologically investigated casestudies to demonstrate the Sasanian landscape in the framework of the“Iranshahr”sociopolitical concept

Association between metformin use and below-the-knee arterial calcification score in type 2 diabetic patients.

BACKGROUND Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk. METHODS The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease. Below-the-knee calcification scores were assessed by computed tomography and supplemented by colour duplex ultrasonography. Data on anti-diabetic drugs were carefully collected from the patients' medical records and during patient interviews. Biochemical and clinical data were studied as potential confounding factors. RESULTS Metformin-treated patients had a significantly lower calcification score than metformin-free patients (mean ± standard deviation: 2033 ± 4514 and 4684 ± 9291, respectively; p = 0.01). A univariate analysis showed that metformin was associated with a significantly lower prevalence of severe below-the-knee arterial calcification (p = 0.02). VC was not significantly associated with the use of other antidiabetic drugs, including sulfonylureas, insulin, gliptin, and glucagon like peptide-1 analogues. A multivariate logistic regression analysis indicated that the association between metformin use and calcification score (odds ratio [95% confidence interval] = 0.33 [0.11-0.98]; p = 0.045) was independent of age, gender, tobacco use, renal function, previous cardiovascular disease, diabetes duration, neuropathy, retinopathy, HbA1c levels, and inflammation. CONCLUSIONS In patients with type 2 diabetes, metformin use was independently associated with a lower below-the-knee arterial calcification score. This association may contribute to metformin's well-known vascular protective effect. Further prospective investigations of metformin's potential ability to inhibit VC in patients with and without type 2 diabetes are now needed to confirm these results

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal

Background: Peripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT. Methods. Eleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%). Results: Reproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI - mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI - mid shaft (ICC 0.99; CV% 3.2). Conclusions: The scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2 nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures