Nonpharmacologic Management of Orthostatic Hypotension in Older People : A Systematic Review. The SENATOR ONTOP Series

The research leading to these results was supported by the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 305930 (SENATOR project). The sponsor did not play any role in the study design, methods, data collection and analysis, and preparation of the article.Peer reviewedPostprin

Using Lean Six Sigma to redesign the supply chain to the operating room department of a private hospital to reduce associated costs and release nursing time to care

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-18, pub-electronic 2021-10-20Publication status: PublishedSeán Paul Teeling - ORCID: 0000-0002-4102-7280 https://orcid.org/0000-0002-4102-7280Continuity of the supply chain is an integral element in the safe and timely delivery of health services. Lean Six Sigma (LSS), a continuous improvement approach, aims to drive efficiencies and standardisation in processes, and while well established in the manufacturing and supply chain industries, also has relevance in healthcare supply chain management. This study outlines the application of LSS tools and techniques within the supply chain of an Operating Room (OR) setting in a private hospital in Dublin, Ireland. A pre-/post-intervention design was employed following the Define, Measure, Analyse, Improve, Control (DMAIC) framework and applying LSS methodology to redesign the current process for stock management both within the OR storage area and within a pilot OR suite, through collaborative, inclusive, and participatory engagement with staff. A set of improvements were implemented to standardise and streamline the stock management in both areas. The main outcomes from the improvements implemented were an overall reduction in the value of stock held within the operating theatre by 17.7%, a reduction in the value of stock going out of date by 91.7%, and a reduction in the time spent by clinical staff preparing stock required for procedures by 45%, all demonstrating the effectiveness of LSS in healthcare supply chain management.18pubpub2

Defining breast cancer awareness and identifying barriers to breast cancer awareness for women with an intellectual disability: A review of the literature

Introduction: Incidence rates for developing breast cancer are similar for women regardless of intellectual ability. However, women with an intellectual disability present with advanced breast cancers, which often have a poor prognosis. Method: A structured narrative review of the literature was performed to explore the concepts of breast awareness and breast cancer awareness and subsequently, identify barriers to breast cancer awareness encountered by women with an intellectual disability. Results: A total of 22 studies involving people with varying levels of intellectual disability informed this review. The barriers to breast cancer awareness encountered by women with an intellectual disability include: lack of their understanding, the role of the carer and literacy issues. Conclusion: Identifying the barriers to breast cancer awareness for women with an intellectual disability will help to facilitate breast cancer awareness which has the potential to result in better long-term outcomes through an early diagnosis of breast cancer

Optimizing drug therapy in patients with advanced dementia: A patient-centered approach

Background: Advanced dementia is a prevalent health problem in geriatric patients. These patients usually suffer from several chronic diseases, frequently leading to an end-of-life situation lasting months or years, generating complex and often inappropriate medication regimens. Objectives: Describe the re-orientation of drug therapy in patients with advanced dementia utilizing a systematic medication review process. Methods: This non-experimental pre-post analysis included all patients with advanced dementia admitted to acute geriatric unit (AGU) over one year. Medications were reviewed by a multidisciplinary team and together with the patient caregivers; new therapeutic objectives based on end-of-life care principles were established. Medications were classified as preventive, therapeutic, or symptomatic. The average number of medications per patient pre- and post-admission was compared. Results: We included 73 patients (mean age 86.1 years, mean Barthel Index: 14.5/100). At admission, patients had a mean of 7.27 drugs compared to 4.82 at discharge (66.85% reduction, P < 0.05). The main drugs withdrawn were cardiovascular and hematological (35.76%). Drugs for prevention decreased by 66.85% (from 1.8 to 0.6, P < 0.05) and those for symptomatic care decreased by 17,52% (from 2.34 to 1.93, P < 0.05). Conclusion: Medication therapy plans in patients with advanced dementia often do not meet their therapeutic goals. The proposed methodology is a useful tool to assess therapeutic appropriateness

Molecular Recognition Effects in Atomistic Models of Imprinted Polymers

In this article we present a model for molecularly imprinted polymers, which considers both complexation processes in the pre-polymerization mixture and adsorption in the imprinted structures within a single consistent framework. As a case study we investigate MAA/EGDMA polymers imprinted with pyrazine and pyrimidine. A polymer imprinted with pyrazine shows substantial selectivity towards pyrazine over pyrimidine, thus exhibiting molecular recognition, whereas the pyrimidine imprinted structure shows no preferential adsorption of the template. Binding sites responsible for the molecular recognition of pyrazine involve one MAA molecule and one EGDMA molecule, forming associations with the two functional groups of the pyrazine molecule. Presence of these specific sites in the pyrazine imprinted system and lack of the analogous sites in the pyrimidine imprinted system is directly linked to the complexation processes in the pre-polymerization solution. These processes are quite different for pyrazine and pyrimidine as a result of both enthalpic and entropic effects

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF)

Effective nebulization of interferon-γ using a novel vibrating mesh.

BACKGROUND: Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. METHODS: Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). RESULTS: Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. CONCLUSIONS: It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ

Deprescribing tool for STOPPFall (screening tool of older persons prescriptions in older adults with high fall risk) items

Background: Health care professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, a deprescribing tool was developed by a European expert group for STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) items. Methods: STOPPFall was created using an expert Delphi consensus process in 2019 and in 2020, 24 panellists from EuGMS SIG on Pharmacology and Task and Finish on FRIDs completed deprescribing tool questionnaire. To develop the questionnaire, a Medline literature search was performed. The panellists were asked to indicate for every medication class a possible need for stepwise withdrawal and strategy for withdrawal. They were asked in which situations withdrawal should be performed. Furthermore, panellists were requested to indicate those symptoms patients should be monitored for after deprescribing and a possible need for follow-ups. Results: Practical deprescribing guidance was developed for STOPPFall medication classes. For each medication class, a decision tree algorithm was developed including steps from medication review to symptom monitoring after medication withdrawal. Conclusion: STOPPFall was combined with a practical deprescribing tool designed to optimize medication review. This practical guide can help overcome current reluctance towards deprescribing in clinical practice by providing an up-to-date and straightforward source of expert knowledge

Carbonic Anhydrase 9 Expression Increases with Vascular Endothelial Growth Factor-Targeted Therapy and Is Predictive of Outcome in Metastatic Clear Cell Renal Cancer

AbstractBackgroundThere is a lack of biomarkers to predict outcome with targeted therapy in metastatic clear cell renal cancer (mccRCC). This may be because dynamic molecular changes occur with therapy.ObjectiveTo explore if dynamic, targeted-therapy-driven molecular changes correlate with mccRCC outcome.Design, setting, and participantsMultiple frozen samples from primary tumours were taken from sunitinib-naïve (n=22) and sunitinib-treated mccRCC patients (n=23) for protein analysis. A cohort (n=86) of paired, untreated and sunitinib/pazopanib-treated mccRCC samples was used for validation. Array comparative genomic hybridisation (CGH) analysis and RNA interference (RNAi) was used to support the findings.InterventionThree cycles of sunitinib 50mg (4 wk on, 2 wk off).Outcome measurements and statistical analysisReverse phase protein arrays (training set) and immunofluorescence automated quantitative analysis (validation set) assessed protein expression.Results and limitationsDifferential expression between sunitinib-naïve and treated samples was seen in 30 of 55 proteins (p<0.05 for each). The proteins B-cell CLL/lymphoma 2 (BCL2), mutL homolog 1 (MLH1), carbonic anhydrase 9 (CA9), and mechanistic target of rapamycin (mTOR) (serine/threonine kinase) had both increased intratumoural variance and significant differential expression with therapy. The validation cohort confirmed increased CA9 expression with therapy. Multivariate analysis showed high CA9 expression after treatment was associated with longer survival (hazard ratio: 0.48; 95% confidence interval, 0.26–0.87; p=0.02). Array CGH profiles revealed sunitinib was associated with significant CA9 region loss. RNAi CA9 silencing in two cell lines inhibited the antiproliferative effects of sunitinib. Shortcomings of the study include selection of a specific protein for analysis, and the specific time points at which the treated tissue was analysed.ConclusionsCA9 levels increase with targeted therapy in mccRCC. Lower CA9 levels are associated with a poor prognosis and possible resistance, as indicated by the validation cohort.Patient summaryDrug treatment of advanced kidney cancer alters molecular markers of treatment resistance. Measuring carbonic anhydrase 9 levels may be helpful in determining which patients benefit from therapy

Heat generation and transfer in automotive dry clutch engagement

Dynamic behaviour of automotive dry clutches depends on the frictional characteristics of the contact between the friction lining material, the flywheel, and the pressure plate during the clutch engagement process. During engagement due to high interfacial slip and relatively high contact pressures, generated friction gives rise to contact heat, which affects the material behaviour and the associated frictional characteristics. In practice excess interfacial slipping and generated heat during torque transmission can result in wear of the lining, thermal distortion of the friction disc, and reduced useful life of the clutch. This paper provides measurement of friction lining characteristics for dry clutches for new and worn state under representative operating conditions pertaining to interfacial slipping during clutch engagement, applied contact pressures, and generated temperatures. An analytical thermal partitioning network model of the clutch assembly, incorporating the flywheel, friction lining, and the pressure plate is presented, based upon the principle of conservation of energy. The results of the analysis show a higher coefficient of friction for the new lining material which reduces the extent of interfacial slipping during clutch engagement, thus reducing the frictional power loss and generated interfacial heating. The generated heat is removed less efficiently from worn lining. This might be affected by different factors observed such as the reduced lining thickness and the reduction of density of the material but mainly because of poorer thermal conductivity due to the depletion of copper particles in its microstructure as the result of wear. The study integrates frictional characteristics, microstructural composition, mechanisms of heat generation, effect of lining wear, and heat transfer in a fundamental manner, an approach not hitherto reported in literature