Results of a multi-site pragmatic hybrid type 3 cluster randomized trial comparing level of facilitation while implementing an intervention in community-dwelling disabled and older adults in a Medicaid waiver

Background: Evidence-based interventions that optimize physical function for disabled and older adults living in the community who have difficulty with daily living tasks are available. However, uptake has been limited, particularly in resource-constrained (Medicaid) settings. Facilitation may be an effective implementation strategy. This study’s aim was to compare internal facilitation (IF) versus IF and external facilitation (EF) on adoption and sustainability of an intervention in a Medicaid home and community-based waiver. Methods: In a hybrid type 3 trial, waiver sites (N = 18) were randomly assigned to implement the intervention using a bundle of strategies with either IF or IF and EF. Adoption and sustainability were assessed via Stages of Implementation Completion (SIC) for each site. Clinician attitudes toward evidence-based practice and self-efficacy were evaluated among 539 registered nurses, social workers, and occupational therapists. Medicaid beneficiary outcomes of activities of daily living, depression, pain, falls, emergency department visits, and hospitalizations were evaluated in a sample of N = 7030 as reflected by electronic health records data of the Medicaid waiver program. Linear mixed-effects models were used to compare outcomes between trial arms while accounting for cluster-randomized design. Results: The mean SIC scores were 72.22 (standard deviation [SD] = 16.98) in the IF arm (9 sites) and 61.33 (SD = 19.29) in the IF + EF arm (9 sites). The difference was not statistically significant but corresponded to the medium clinically important effect size Cohen’s d = 0.60. Clinician implementation outcomes of attitudes and self-efficacy did not differ by trial arm. Beneficiary depression was reduced significantly in the IF + EF arm compared to the IF arm (p = .04, 95% confidence interval for the difference [0.01, 0.24]). No differences between trial arms were found for other beneficiary outcomes. Conclusions: Level of facilitation did not enhance capacity for adoption and sustainability of an evidence-based intervention in a Medicaid setting that cares for disabled and older adults. Improved beneficiary depression favored use of IF and EF compared to IF alone, and no differences were found for other outcomes. These findings also suggest level of facilitation may not have impacted beneficiary outcomes

Mechanochemistry of von Willebrand factor

AbstractVon Willebrand factor (VWF), a blood multimeric protein with a very high molecular weight, plays a crucial role in the primary haemostasis, the physiological process characterized by the adhesion of blood platelets to the injured vessel wall. Hydrodynamic forces are responsible for extensive conformational transitions in the VWF multimers that change their structure from a globular form to a stretched linear conformation. This feature makes this protein particularly prone to be investigated by mechanochemistry, the branch of the biophysical chemistry devoted to investigating the effects of shear forces on protein conformation. This review describes the structural elements of the VWF molecule involved in the biochemical response to shear forces. The stretched VWF conformation favors the interaction with the platelet GpIb and at the same time with ADAMTS-13, the zinc-protease that cleaves VWF in the A2 domain, limiting its prothrombotic capacity. The shear-induced conformational transitions favor also a process of self-aggregation, responsible for the formation of a spider-web like network, particularly efficient in the trapping process of flowing platelets. The investigation of the biophysical effects of shear forces on VWF conformation contributes to unraveling the molecular mechanisms of many types of thrombotic and haemorrhagic syndromes

Engaging caregivers to use an evidence‑based intervention for medicaid benefciaries with Alzheimer’s disease: a pilot study

Background This pilot study aimed to adapt an intervention, engaging informal caregivers to help clinicians with providing care to improve (or maintain) physical function of individuals with Alzheimer’s Disease or other dementias. To the best of our knowledge, for the frst time, we report on use of the intervention in those with Alzheimer’s Disease or other dementias. Methods This was a 5-month mixed methods cohort study in a convenience sample of clinicians, caregivers, and benefciaries at 3-Medicaid Home and Community-based Service sites in Michigan. Two content experts and 5 caregivers modifed the intervention. We trained 116 clinicians to engage caregivers and 50 caregivers to help clinicians provide the modifed intervention to 52 benefciaries with Alzheimer’s Disease or other dementias. Thematic analyses, descriptive statistics, counts, proportion comparisons, t-tests, and McNemar’s tests were used to examine socio-demographics, clinician knowledge uptake and satisfaction with training and use of the intervention; caregiver self-efcacy, feasibility, acceptability, usability, and satisfaction with intervention and benefciary outcomes (pre-/post). Results Feasibility (enrolled/recruited=78.5–86.7%), acceptability (7.55–8.35 [SD 1.50–2.06]), and usability (7.85–8.81 [SD 1.50–2.6]) of the modifed intervention (1=low;10=high) were high. Pre-/post-intervention clinician knowledge (12.33–12.28, SD 1.80–2.84; -0.52, SD 1.95) was high. Caregiver self-efcacy increased (0.81 [SD 0.62] p\u3c0.01). Benefciary outcomes did not improve nor decline (\u3e0.05). Conclusions Engaging informal caregivers to assist clinicians with providing an intervention adapted to the needs of those with Alzheimer’s Disease or other dementias was feasible, acceptable, and usable. Further testing in a broader sample of those with dementia in various settings is needed

A standardized postmortem protocol to assess the real burden of sudden infant death syndrome

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Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?

: Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. Methods: A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Results: Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. Conclusions: The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma

Prevalence, molecular epidemiology and intra-hospital acquisition of Klebsiella pneumoniae strains producing carbapenemases in an Italian teaching hospital from January 2015 to September 2016.

Objectives: We described Klebsiella pneumoniae producing carbapenemase (CPKP) spread from 01/01/2015 to 13/09/16 in a tertiary level hospital. Methods: The first positive surveillance rectal swab (SRS) or clinical sample (CS) collected in the medical department (MD), surgical department (SD) and intensive care department (ICD) were included in the study. A validated in-house Real-Time PCR method was used to detect carbapenemases; multilocus sequence typing (MLST) was used for further characterization of the strains. Results: 21535 patients were included: 213 CPKP strains from surveillance rectal swab (SRS) and 98 from clinical samples (CS) were collected. The percentage of CPKP detected in SRS with respect to CS increased in the medical MD from 2015 to 2016 (p = 0.01) and in ICD from 2012 to 2015 (p = 0.0001), while it decreased in SD from 2014 to 2016 (p = 0.003); 68.5% of the positive SRS had a previous negative SRS; CPKP was more frequently identified in CS than in SRS in MD. Twelve strains harboured more than one carbapenemase gene. Many other species harbouring a carbapenemase gene were collected. Conclusions: MDs need more inclusive surveillance criteria. The late detection of positive SRS underlined the risk of colonization during hospitalization

Intra-hospital acquisition of colonization and infection by Klebsiella pneumoniae strains producing carbapenemases and carriage evolution: A longitudinal analysis in an Italian teaching hospital from January 2017 to August 2019

Abstract Objectives We present an updated picture (1/1/2017–31/08/2019) of the frequency of carbapenemase producing Klebsiella pneumoniae (CPKP) in surveillance rectal swabs (SRS) and in clinical samples (CS) of patients admitted to a tertiary level hospital, focusing on longitudinal evolution of CPKP detected in SRS and on colistin resistant strains. Methods Retrospective longitudinal analysis. Only the first positive CPKP strain isolated from each patient was included. Results 638 CPKP strains were identified (471 in SRS and 167 in CS). SRS frequency increased over time in the medical department, remained high in the surgical department (SD) and decreased in the intensive care department. Most SRS–71.3%–and 49.1% of CS had nosocomial origin; about half of the SRS were identified in the SD. Regarding SRS evolution, carriage was confirmed in 39.5% of patients, no more testing in 25.5%, clinical involvement in 24.8 %, and negative result in 10.2%. Rates of colistin resistance were 20.1% in 2017, 31.2% in 2018 and 26.9% in 2019. Conclusions CPKP diffusion is still an important issue despite the surveillance program. It is vital to enhance medical staff's awareness on this because most CPKP first detections in SRS occurred during hospital stay due to a nosocomial acquisition with a comparable picture over time. Colistin resistance is increasing

Viral infections of the central nervous system in elderly patients: a retrospective study

Summary Objectives Very few data exist on viral meningitis and encephalitis in elderly patients (>65 years old). Methods This study investigated the detection of herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes virus 6 (HHV-6), HHV-7, HHV-8, cytomegalovirus (CMV), Epstein–Barr virus (EBV), enterovirus (EV), human adenovirus (HAdV), human parechoviruses (HPeVs), and tick-borne encephalitis virus (TBEV) through real-time PCR (RT-PCR) in patients >65 years old who had cerebrospinal fluid (CSF) tested for a suspected central nervous system infection. Results A total of 2868 RT-PCRs were performed on 502 CSF samples. Overall, 65 positive RT-PCRs were found: 23 for HSV (35.4% of positives), 15 for EV (23.1% of positives), 14 for EBV (21.5% of positives), 12 for VZV (18.5% of positives), and one for CMV (1.5% of positives). A positive RT-PCR in CSF was detected in 24 (17.4%) patients aged ≥80 years and in 35 (9.6%) patients aged 65–79 years ( p =0.02). VZV was more frequently detected in the oldest subjects (5.9% vs. 1.6%, p =0.03). Conclusions HSV was the most common viral aetiology identified in the study, with VZV infection being recognized more frequently in those patients aged ≥80 years

Pathogenesis Of Portal Vein Thrombosis In Liver Cirrhosis: The Role of the ADAMTS13/VWF Unbalance

Increasing evidence shows a potential role of ADAMTS13 deficiency as a risk factor for the high prevalence of portal vein thrombosis (PVT) in cirrhotic patients. This deficiency, due to myofibroblastic transformation of hepatic stellate cells (HSCs), the source of ADAMTS13, is responsible for the prevalence of ultra large molecular weight multimers of von Willebrand factor (UL-VWF) in the hepatic microcirculation. This phenomenon would favor the prohaemostatic function of VWF, which, together with an elevation of coagulation FVIII, which is associated to VWF, could sustain microcirculatory thrombosis in the liver. These phenomena, triggering an increase of the intra-hepatic pressure, would cause a slowdown of the portal flow, favoring the occurrence of PVT. Although this scenario is justified by retrospective observational clinical studies, it will be mandatory to clarify the ADAMTS13 expression in HSCs associated with the activity of plasma ADAMTS13 in different stage of liver diseases. Hence, a prospective clinical trial (ClinicalTrials.gov Identifier: NCT03322696) is ongoing to unravel the linkage between all the actors involved in the complex phenomenon of PVT occurring in cirrhosi