Drug–Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications

Peripheral vestibular disease can be treated with several approaches (e.g., maneuvers, surgery, or medical approach). Comorbidity is common in elderly patients, so polytherapy is used, but it can generate the development of drug–drug interactions (DDIs) that play a role in both adverse drug reactions and reduced adherence. For this reason, they need a complex kind of approach, considering all their individual characteristics. Physicians must be able to prescribe and deprescribe drugs based on a solid knowledge of pharmacokinetics, pharmacodynamics, and clinical indications. Moreover, full information is required to reach a real therapeutic alliance, to improve the safety of care and reduce possible malpractice claims related to drug–drug interactions. In this review, using PubMed, Embase, and Cochrane library, we searched articles published until 30 August 2021, and described both pharmacokinetic and pharmacodynamic DDIs in patients with vestibular disorders, focusing the interest on their clinical implications and on risk management strategies.

Racial Differences in the Effect of Alzheimer’s Disease on Adherence to Medication Therapy for Chronic Diseases

Multiple dementia (the presence of one or more types of dementia in a single individual) and multi-morbidity (the presence of multiple chronic diseases in an individual) present a major challenge to the U.S. healthcare system. The reduction in cognitive function associated with neurocognitive disorders such as Alzheimer’s Disease (AD) and Related Dementias (ADRD) reduce the ability of the affected individual to take care of him/herself. This can manifest as reduced adherence to medication regimens designed to manage other chronic conditions, in reduced ability to engage in healthy behavior such as exercise, or in other ways. The result is an increase in the probability of otherwise avoidable adverse health outcomes and related healthcare costs. In this study, we showcase two high impact chronic conditions common in the elderly: hypertension and type 2 diabetes mellitus (T2D). Using a 5% sample of the total Medicare population we identify groups of individuals with AD/ADRD and i) hypertension, ii) T2D or iii) both. Each group is then propensity-score-matched to similar individuals with hypertension, T2D or both but without a diagnosis of AD/ADRD. The primary explanatory variable of interest is the medication possession ratio (MPR) calculated at 1-year intervals for prescribed diabetes and/or hypertension medications. MPRs were compared between the two groups using t-tests and standardized differences each year after baseline and until death/censoring. A Cox proportional hazard model was then used to estimate differences in survival between these two groups and across race/ethnicity-related strata. Reduced adherence with time and notable race/ethnicity-related differences were identified.

Behavioral Implications in COVID-19 Spread and Vaccinations

COVID-19 vaccinations have been administered quickly in the USA. However, a surprisingly large number of Americans are unwilling to get vaccinated. Without enough people getting vaccinated, the pandemic will not end. The longer the pandemic persists, the more opportunities exist for more virulent strains to emerge. This model looks at the effects of people’s behavior in containing and ending the COVID-19 pandemic in the USA. Human behavior adds several feedback loops to the standard SEIR model. Comparisons are made between cases with and without behavior loops, with reduced adherence to the recommended or mandated masks and social distancing, with and without the vaccine, and the effects of an early mask mandate termination. The results suggest human behavior must be accounted for in epidemiology models and that removing masks before enough vaccine are administered not only puts those vaccinated at risk, but allows the disease to readily spread again.

Interplay between COVID-19 vaccines and social measures for ending the SARS-CoV-2 pandemic

Background: The development and authorization of COVID-19 vaccines has provided the clearest path forward to eliminate community spread and thus end the ongoing SARS-CoV-2 pandemic. However, the limited pace at which the vaccine can be administered motivates the question, to what extent must we continue to adhere to social intervention measures such as mask wearing and social distancing? Methods: We develop a mathematical model of COVID-19 spread incorporating both vaccine dynamics and socio-epidemiological parameters. We use this model to study two important measures of disease control and eradication, the effective reproductive number Rt and the peak intensive care unit (ICU) caseload, over three key parameters: social measure adherence, vaccination rate, and vaccination coverage. Results: Our results suggest that, due to the slow pace of vaccine administration, social measures must be maintained by a large proportion of the population until a sufficient proportion of the population becomes vaccinated for the pandemic to be eradicated. By contrast, with reduced adherence to social measures, hospital ICU cases will greatly exceed capacity, resulting in increased avoidable loss of life. We then investigate the threat of localized outbreaks in low-vaccinated populations that have removed all social intervention mandates, and show that such populations could remain highly susceptible to major outbreaks particularly in the face of more easily transmissible variants. Conclusions: These findings highlight the complex interplay involved between vaccination and social protective measures, and indicate the practical importance of continuing with extant social measures while vaccines are scaled up to allow the development of the herd immunity needed to end or control SARS-CoV-2 sustainably.

Palatability and Swallowability of Pimavanserin When Mixed with Selected Food Vehicles: An Exploratory Open-Label Crossover Study

Dysphagia (difficulty swallowing) affects up to 13% of persons 65 years and older and 51% of older persons in nursing homes and can contribute to reduced adherence to oral medications. This was an exploratory, single-center, open-label, randomized, crossover study in healthy older adult participants. Primary objectives were evaluation of palatability (taste) and swallowability of the contents of pimavanserin 34 mg capsules mixed with selected soft foods or a liquid nutritional supplement. Secondary objectives included evaluation of additional palatability endpoints and ease of capsule manipulation for mixing. A total of 18 healthy, older adult participants (mean age 65 years) were included. Mean participant ratings for all food vehicles were “moderately like” to “neither like nor dislike” for palatability and “very easy” to “somewhat easy” for swallowability. Capsule manipulation to allow sprinkling of contents was rated “very easy” or “somewhat easy” by most participants. There were five treatment-emergent adverse events, all mild; two were deemed related to study treatment. The palatability and swallowability of pimavanserin was considered acceptable when administered with certain soft foods or a liquid nutritional supplement by the study participants.

High but not low self-reported statin adherence was confirmed by a novel method based on plasma-statin measurements in coronary outpatients

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helse Sør-Øst Background To what extent self-reported adherence measures correspond with directly measured statin adherence is unknown. Purpose To determine the relationship between, self-reported adherence measures, low density lipoprotein-cholesterol (LDL-C) and directly measured statin adherence in coronary outpatients. Methods Patients on atorvastatin (N = 373) participated in a cross-sectional study median 16 months after a coronary event. Adherence to statins the past 7 days, general medication adherence assessed by the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi adherence question was obtained by a self-report questionnaire. Atorvastatin was determined in spot blood plasma samples by a novel liquid-chromatography tandem mass-spectrometry method discriminating between adherence (0-1 doses omitted) and reduced (≥2 doses omitted) adherence. Participants were unaware of the atorvastatin analyses at study participation. Results Mean age was 63 (SD 9) years and 19% were females. Mean atorvastatin dose was 64 (SD 21) mg. The number with reduced adherence by the different measurement methods, Cohens kappa agreement score between the self-reported and direct adherence measures, and LDL-C are shown in the Table. Statin adherence was confirmed by the direct method among 96% reporting high statin adherence the past 7 days, among 95% reporting high adherence on the MMAS-8 and among 94% reporting high adherence on the Gehi adherence question. In contrast, among patients classified with reduced statin adherence by the direct method, only 40% reported reduced statin adherence the past week, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi adherence question. Conclusions The direct method confirmed high, but not low, self-reported statin adherence in this selected sample of coronary outpatients. In patients with elevated LDL-cholesterol, plasma-statin measurements emerges as a potential improvement for clinical statin management. Adherence measures and LDL cholesterol Directly measured atorvastatin adherence Self-reported statin adherence past 7 days Self-reported medication adherence past month (Gehi) 8-item Morisky medication adherence scale Number with reduced adherence, % 7.8 5.5 3.0 8.4 Cohen"s kappa (95% CI) Reference 0.4 (0.2 to 0.6) 0.3 (0.1 to 0.5) 0.2 (0.1 to 0.4) LDL-C, Adherent, mean (95% CI) 1.9 (1.8 to 1.9) 1.9 (1.8 to 2.0) 1.9 (1.8 to 2.0) 1.9 (1.8 to 1.9) LDL-C, Reduced adherence, mean (95% CI) 2.8 (2.4 to 3.2) 2.8 (2.3 to 3.2) 3.2 (2.5 to 3.8) 2.1 (1.9 to 2.4) LDL-C, Adherent versus reduced adherence P <0.001 P = 0.001 P = 0.004 P = 0.07 Agreement between directly measured atorvastatin adherence, self-reported measures of adherence, and mean low density lipoprotein-cholesterol (LDL-C)

Polypharmacy in elderly people: epidemiology, consequences and prevention strategies

Aging is a status often associated with multiple comorbidities which require pharmacologic intervention and complex medication regimens. Aging population results to the increase of chronic diseases and subsequent comorbidities that require concomitant multiple medications. It is reported that about 80 % of elderly have at least one chronic condition, and about half of them have at least two (such as heart disease, hypertension, diabetes mellitus, arthritis, and cancer). According the literature the worldwide polypharmacy prevalence has a wide range (between 5 to 78 %) due to different definitions on the number of medications taken (ranging between 2 and 9) and the different samples studied. In most studies polypharmacy was more common between women and in more elderly people. Many multicenter studies have been performed to define the term of polypharmacy and its prevalence in the elderly population. Polypharmacy is of growing concern for the older adults, because it can be very dangerous for this population due to altered absorption, distribution, metabolism and excretion of the drugs within their body reflecting unexpected pharmacokinetics and pharmacodynamics of various medications. This fact can lead to adverse drug reactions (ADR), drug interactions, noncompliance and reduced adherence, reduced functional status, geriatric syndromes, high risk of hospitalization and possible death. Over the last decade, there are several evaluation tools which can help the General Practitioner prevent the polypharmacy in the elderly. As prescribing for this group of individuals is a very challenging procedure, the General Practitioner should balance between under-treatment, over-treatment and risks and benefits. This review concluded that we need more cross-sectional clinical studies on practical preventive interventions to be applied not only on the population which is already exposed to polypharmacy, but also to the general population.

Pediatric routine vaccinations in the COVID 19 lockdown period: the survey of the Italian Pediatric Society

Background COVID-19 pandemic was responsible for disrupting routine immunization activities all over the world. Aim of the study was to investigate the reduced adherence to the national children vaccination schedule during the lockdown period in Italy. Materials and methods Through social channels, the Italian Pediatric Society conducted a survey among Italian families on children vaccination during lockdown period. Results In the study period, 1474 responders were collected. More than one third (34%) of them skipped the vaccine appointment as they were afraid of SARS-CoV-2-virus (44%), vaccination services postponed the appointment (42%) or was closed to public (13%). Discussion Reduction in routine immunization coverage may represent a serious life-threating problem for unvaccinated or under-vaccinated children. Conclusions Information on national and local preventive measures including physical distancing, handwashing, and proper coughing/sneezing hygiene should be spread among families in order to contrast vaccine hesitancy and maintain adequate coverage levels during COVID19 pandemic period.

IRF4 deficiency vulnerates B progeny for leukemogenesis via Jak3 mutations resembling Ph-like B-ALL in humans

How disturbances of B cell development provoke adult B acute lymphoblastic leukemia (B-ALL) remains poorly understood. Here we describe Irf4–/– mice as prone to developing B-ALL with age. Irf4–/– pro/preB cells exhibited impaired differentiative but enhanced proliferative potential in vitro and accumulated in spleens of healthy Irf4–/– mice, suggesting reduced adherence to the IL-7 providing bone marrow niche. Thus selected, pro/preB cells transformed acquiring proliferative IL-7 independency through Jak3 gain-of-function mutations. Targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4–/– leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. As low IRF4 expression and JAK3 mutations also characterize a subpopulation of Ph-like B-ALL in adult humans, our results imply Irf4–/– mice as a suitable model for investigating preleukemic conditions in adults. Using this model, we identified an unexpected effect of Ruxolitinib treatment in B-ALL.

Antibodies against dextransucrase from Streptococcus mutans display anti-biofilm and growth suppressing activities

Dextransucrase produced by Streptococcus mutans play an essential role in the formation of dental caries by synthesizing exopolysaccharides from sucrose, an important metabolite of the organism. In this study we report the location of dextransucrase in Streptococcus mutans cells and describe that antibodies raised against dextransucrase inhibited biofilm formation and reduced the adherence and hydrophobic properties of Streptococcus mutans. Western blot analysis and immunoelectron microscopy revealed that dextransucrase is located abundantly in the membrane fraction in S. mutans cells. Scanning electron microscopy and fluorescence microscopy revealed reduced cell density, impaired bioflim (plaque) formation in presence of dextransucrase antibodies. Genes associated with bioflim formation in S. mutans such as GtfB, GtfC, BrpA, relA, Smu630, vicK were down regulated (50–97%) in presence of the enzyme antibody. Presence of enzyme antibodies reduced adherence of S. mutans cells to glass surfaces by 58% and hydrophobicity by 55.2%. However dextransucrase antibodies did not affect acid production by S. mutans, under the experimental conditions. Immunohistochemistry studies with certain human samples displayed no cross reactivity with dextransucrase antibody. These findings suggest that antibodies against dextransucrase exhibit a profound inhibitory effect on the vital cariogenic factors of S. mutans and have no cross reactivity with human tissues tested, thus implying that dextransucrase could be a promising antigen to study its anticariogenic potential.