Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review

ObjectivesSeveral implementation strategies can reduce potentially inappropriate medication (PIM) prescribing. Although use of PIMs has declined in recent years, it remains prevalent. Various strategies exist to improve the appropriateness of medication use. However, little is known about the processes of these different implementation strategies. This scoping review aims to investigate how the process evaluation of implementation strategies for reducing PIM prescribing in the older population has been studied.MethodsWe searched for process evaluations of implementation strategies for reducing PIM prescribing in PUBMED, SCOPUS and Web of Science published between January 2000 and November 2019 in English. We applied the following inclusion criteria: patients aged ≥65 years, validated PIM criteria, and implementation process evaluated. The review focuses on decision support for health care professionals. We described the findings of the process evaluations, and compared the authors’ concepts of process evaluation of the included publications to those of Proctor et al.( 2010).ResultOf 9131 publications screened, 29 met our inclusion criteria. Different process evaluation conceptualizations were identified. Most process evaluations took place in the initial stages of the process (acceptability, adoption, appropriateness, and feasibility) and sustainability and implementation costs were seldom evaluated. None of the included publications evaluated fidelity.Multifaceted interventions were the most studied implementation strategies. Medication review was more common in acceptability evaluations, multidisciplinary interventions in adoption evaluations, and computerized systems and educational interventions in feasibility evaluations. Process evaluations were studied from the health care professionals’ viewpoint in most of the included publications, but the management viewpoint was missing.DiscussionThe conceptualization of process evaluation in the field of PIM prescribing is indeterminate. There is also a current gap in the knowledge of sustainability and implementation costs. Clarifying the conceptualization of implementation process evaluation is essential in order to effectively translate research knowledge into practice.     

Interventions in the diagnosis and adoption of pacemaker therapy in sinus node dysfunction patients: Results from the IMPROVE Brady study

AimsIMPROVE Brady assessed whether a process improvement intervention could increase adoption of guideline-based therapy in sinus node dysfunction (SND) patients.Methods/Results: IMPROVE Brady was a sequential, prospective, quality improvement initiative conducted in India and Bangladesh. Patients with symptomatic bradycardia were enrolled. In Phase I, physicians assessed and treated patients per standard care. Phase II began after implementing educational materials for physicians and patients. Primary objectives were to evaluate the impact of the intervention on SND diagnosis and pacemaker (PPM) implant. SF-12 quality of life (QoL) and Zarit burden surveys were collected pre- and post-PPM implant.A total of 978 patients were enrolled (57.7 ± 14.8 years, 75% male), 508 in Phase I and 470 in Phase II. The diagnosis of SND and implantation of PPM increased significantly from Phase I to Phase II (72% vs. 87%, P < 0.001 and 17% vs. 32%, P < 0.001, respectively). Pacemaker implantation was not feasible in 41% of patients due to insurance/cost barriers which was unaltered by the intervention. Both patient QoL and caregiver burden improved at 6-months post-PPM implant (P < 0.001).ConclusionsA process improvement initiative conducted at centers across India and Bangladesh significantly increased the diagnosis of SND and subsequent treatment with PPM therapy despite the socio-economic constraints.     

Factors determining phage stability/activity: challenges in practical phage application

Introduction: Phages consist of nucleic acids and proteins that may lose their activity under different physico-chemical conditions. The production process of phage formulations may decrease phage infectivity. Ingredients present in the preparation may influence phage particles, although preparation and storage conditions may also cause variations in phage titer. Significant factors are the manner of phage application, the patient’s immune system status, the type of medication being taken, and diet.

Areas covered: We discuss factors determining phage activity and stability, which is relevant for the preparation and application of phage formulations with the highest therapeutic efficacy. Our article should be helpful for more insightful implementation of clinical trials, which could pave the way for successful phage therapy.

Expert opinion: The number of naturally occurring phages is practically unlimited and phages vary in their susceptibility to external factors. Modern methods offer engineering techniques which should lead to enhanced precision in phage delivery and anti-bacterial activity. Recent data suggesting that phages may also be used in treating nonbacterial infections as well as anti-inflammatory and immunomodulatory agents add further weight to such studies. It may be anticipated that different phage activities could have varying susceptibility to factors determining their actions.     

Semi-perfusion cultures of suspension MDCK cells enable high cell concentrations and efficient influenza A virus production

Control and prevention of rapid influenza spread among humans depend on the availability of efficient and safe seasonal and pandemic vaccines, made primarily from inactivated influenza virus particles. Current influenza virus production processes rely heavily on embryonated chicken eggs or on cell culture as substrate for virus propagation. Today’s efforts towards process intensification in animal cell culture could innovate viral vaccine manufacturing using high-yield suspension cells in high cell density perfusion processes. In this work, we present a MDCK cell line adapted to grow as single cell suspension with a doubling time of less than 20 h, achieving cell concentrations over 1 × 10⁷ cells/mL in batch mode. Influenza A virus titer obtained in batch infections were 3.6 log₁₀(HAU/100 µL) for total- and 10⁹ virions/mL for infectious virus particles (TCID₅₀), respectively. In semi-perfusion mode concentrations up to 6 × 10⁷ cells/mL, accumulated virus titer of 4.5 log₁₀(HAU/100 µL) and infectious titer of almost 10¹⁰ virions/mL (TCID₅₀) were possible. This exceeds results reported previously for cell culture-based influenza virus propagation by far and suggests perfusion cultures as the preferred method in viral vaccine manufacturing.     

Forced Oxidative Degradation Pathways of the Imidazole Moiety of Daclatasvir

Daclatasvir hydrochloride (DCV) is the active pharmaceutical ingredient of Daklinza, a marketed product for the treatment of hepatitis C viral infection. The intrinsic stability of daclatasvir was evaluated via a forced degradation study. DCV was found to be stable in the solid state. In solution, its carbamate moiety is susceptible to basic hydrolysis, whereas its imidazole is liable to base-mediated autoxidation to form degradants 1 and 3, 7-8, respectively. The imidazole moiety can also be oxidized to form degradants 6-7 in the presence of hydrogen peroxide or azobisisobutyronitrile. The chloro-adduct degradant 9 was also observed in hydrogen peroxide solution. Furthermore, the imidazole moiety is sensitive to photodegradation in solution. Degradants 2-8 were observed in a solution of DCV exposed to high intensity light/UV light; the formation of degradants 2 and 5-8 was postulated through 4 degradation pathways. The degradants 3 and 4 were deemed to be secondary degradants of 7 and 5, respectively.     

Burnett Order Stress and Spatially-Dependent Boundary Conditions for the Lattice Boltzmann Method

Stress boundary conditions for the lattice Boltzmann equation that are consistent to Burnett order are proposed and imposed using a moment-based method. The accuracy of the method with complicated spatially-dependent boundary conditions for stress and velocity is investigated using the regularized lid-driven cavity flow. The complete set of boundary conditions, which involve gradients evaluated at the boundaries, are implemented locally. A recently-derived collision operator with modified equilibria and velocity-dependent collision rates to reduce the defect in Galilean invariance is also investigated. Numerical results are in excellent agreement with existing benchmark data and exhibit second-order convergence. The lattice Boltzmann stress field is studied and shown to depart significantly from the Newtonian viscous stress when the ratio of Mach to Reynolds numbers is not negligibly small.     

Oligo-monocytic CMML and other pre-CMML states: Clinical impact,prognostication and management

Chronic myelomonocytic leukemia (CMML) is defined by myelodysplasia, pathologic accumulation of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). In recent years, minimal diagnostic criteria for classical CMML and CMML-variants were proposed. Moreover, potential pre-stages of CMML and interface conditions have been postulated. Oligomonocytic CMML is a condition where the absolute peripheral blood monocyte count does not reach a diagnostic level but all other criteria for CMML are fulfilled. Among potential pre-stages of CMML, clonal and non-clonal conditions have been described, including idiopathic monocytosis (IMUS) and clonal monocytosis of unknown significance (CMUS). Patients with myelodysplastic syndromes (MDS), clonal cytopenia of unknown significance (CCUS), clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) may also progress to CMML. The current article provides an overview of pre-CMML conditions and oligomonocytic CMML, with special reference to diagnostic criteria, differential diagnoses, clinical outcomes and management.