The Nocebo Effect.

Adverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experiencing negative outcomes, and other contextual and environmental factors. As research advances over the years, mechanistic knowledge is accumulating on the neurobiological mechanisms of nocebo effects. This review summarizes studies on different facets of nocebo effects and responses and discusses clinical implications, ethical considerations, and future directions.

Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes-results from the NOR-Gout study.

OBJECTIVES: Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. METHODS: Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate >360 µmol/L. Patients (mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi) attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5-25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication. RESULTS: At 5-years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22-25). Patients in the lowest MARS-5 quartile had, compared to the highest quartile, more often a flare during the last year of follow-up (33.3% vs. 9.5%, P=0.004), and reached the 5-yr serum urate treatment target less frequently (45.2% vs. 87.5%, P<0.001). Baseline lower age (OR 0.56, 95%CI 0.39-0.79), non-European origin (OR 0.22, 95%CI 0.06-0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91-0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58-0.92) were independent risk factors for non-adherence to medication. CONCLUSIONS: Patients reported after 5 years high adherence to medication. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.

Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam.

PURPOSE: Standard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC. PATIENTS AND METHODS: In 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires. RESULTS: 54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32-3.98, P = 0.003; OR = 4.36, 95% CI = 0.95-19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08-3.55, P = 0.024; OR = 1.86, 95% CI = 1.1-3.14, P = 0.02; OR = 2.34, 95% CI = 1.29-4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001). CONCLUSIONS: This study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

Pattern and predictors of non-adherence to diabetes self-management recommendations among patients in peripheral district of Bangladesh.

OBJECTIVES: This study was designed to determine the extent of non-adherence to the different dimensions of diabetes self-management and to identify the factors influencing non-adherence among peripheral patients in Bangladesh. METHODS: A cross-sectional study was conducted among 990 adult diabetic patients residing in Thakurgaon district, Bangladesh. Data were collected through face-to-face interviews including socio-demographic information, disease and therapeutic, health services, knowledge and adherence to self-management components. RESULTS: The proportion of non-adherence to drug prescription was 66.7%, dietary regimen (68.9%), physical exercise (58.0%), follow-up visit/blood glucose test (88.2%), stopping tobacco (50.6%), and regular foot care (93.9%). Significant predictors for non-adherence to drug were poorest socio-economic status (OR = 2.47), absence of diabetic complications (OR = 1.43), using non-clinical therapy (OR = 5.61), and moderate level of knowledge (OR = 1.87). Non-adherence to dietary recommendations was higher for women (OR = 1.72), poorest socio-economic status (OR = 3.17), and poor technical knowledge (OR = 4.68). Non-adherence to physical exercise was lower for women (OR = 0.62), combined family (OR = 0.63), middle socio-economic status (OR = 0.54), and moderate knowledge on physical exercise (OR = 0.55). Non-adherence to follow-up visits/blood glucose test was higher among patients who did not have diabetic complications (OR = 1.81) and with own transport (OR = 2.57), and respondents from high-income group (OR = 0.23) were less likely to be non-adherent. Non-adherence to stopping tobacco was higher for older individuals (OR = 1.86); but lower for women (OR = 0.48), individuals with higher education level (OR = 0.17) and patients sick for a longer time (OR = 0.52). Non-adherence to foot care was higher for patients who needed longer time to go to hospital (OR = 4.07) and had poor basic knowledge on diabetes (OR = 17.80). CONCLUSION: An alarmingly high proportion of diabetic patients did not adhere to diabetes self-management. Major predictors for non-adherence were related to patient's demographic characteristics and their experience with disease, treatment and health care services.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Validating methods used to identify non-adherence adverse drug events in Canadian administrative health data.

AIMS: Medication non-adherence is a type of adverse drug event that can lead to untreated and exacerbated chronic illness, and that drives healthcare utilization. Research using medication claims data has attempted to identify instances of medication non-adherence using the proportion of days covered or by examining gaps between medication refills. We sought to validate these measures compared to a gold standard diagnosis of non-adherence made in hospital. METHODS: This was a retrospective analysis of adverse drug events diagnosed during three prospective cohorts in British Columbia between 2008 and 2015 (n = 976). We linked prospectively identified adverse drug events to medication claims data to examine the sensitivity and specificity of typical non-adherence measures. RESULTS: The sensitivity of the non-adherence measures ranged from 22.4% to 37.5%, with a proportion of days covered threshold of 95% performing the best; the non-persistence measures had sensitivities ranging from 10.4% to 58.3%. While a 7-day gap was most sensitive, it classified 61.2% of the sample as non-adherent, whereas only 19.6% were diagnosed as such in hospital. CONCLUSIONS: The methods used to identify non-adherence in administrative databases are not accurate when compared to a gold standard diagnosis by healthcare providers. Research that has relied on administrative data to identify non-adherent patients both underestimates the magnitude of the problem and may label patients as non-adherent who were in fact adherent.

The impacts of undetected nonadherence in phase II, III and post-marketing clinical trials: An overview.

AIMS: This research aims to provide an overview of the consequences of undiagnosed nonadherence (noninitiation, suboptimal implementation, nonpersistence) in randomized clinical trials (RCTs). METHODS: This research was conducted by combining a literature review and qualitative semistructured interviews with key opinion leaders. Based on this groundwork, the consequences of undiagnosed nonadherence in RCTs were summarized and reported in a figure. This study focused on phases II, III and post-marketing in ambulatory settings across a variety of therapeutic areas and indications. RESULTS: Various consequences of nonadherence in RCTs were investigated. In phase II, drug efficacy may be underestimated, variability in the outcomes may be high and a distorted picture of side effects could be reported, resulting in an uncertain impression of the investigational product's profile and complicating decision-making. The sponsor may need to increase the sample size of the upcoming phase III study to improve its power, representing additional costs, or even terminate the study. In phase III, similar phenomena may be observed, making demonstration of efficacy to the regulatory bodies more difficult. Lastly, after commercialization, a distortion in pharmacometrics may occur: the drug may underperform, prescriptions may be refilled less often than expected or extra expenses may be incurred by the payers. This can result in post-marketing dose reduction, new competitors coming into the market and, eventually, product withdrawal. CONCLUSIONS: This research highlighted the many potential adverse consequences of undiagnosed nonadherence in RCTs, including additional costs. Collecting accurate data appeared to be crucial for decision-making throughout the drug development process.

The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta-analysis.

BACKGROUND: Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic-induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously. METHOD: A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness. A meta-analysis was also completed where applicable. RESULTS: We identified two categories of studies for the meta-analysis. Category 1 included three studies, which compared measures of AP adherence or discontinuation across BMI classes/degrees of self-reported weight gain. When compared to normal weight individuals receiving APs or those who did not report AIWG, individuals who were either overweight or obese or reported weight gain in relation to AP use had an increased odds of AP nonadherence (OR 2.37; 95% CI 1.51-3.73; p = 0.0002). Category 2 had 14 studies which compared measures of discontinuation related to weight gain reported as an adverse effect across different APs. Olanzapine was associated with a 3.32 times (95% CI 2.32-4.74; p < 0.00001) increased likelihood of nonadherence or discontinuation when compared to other APs with lower weight gain liabilities. Similarly, APs with moderate weight gain liability (paliperidone, risperidone, and quetiapine) increased the odds of nonadherence or discontinuation by 2.25 (95% CI 1.31-3.87; p = 0.003) when compared to APs considered to have lower weight gain liability (i.e. haloperidol and aripiprazole). The qualitative summary also confirmed these findings. CONCLUSION: This review and meta-analysis suggests that AIWG influences medication nonadherence/discontinuation, whereby APs with higher weight gain liability are associated with nonadherence/discontinuation. Additional studies are needed to confirm these findings.

Non-Adherence to Anti-Retroviral Therapy Among Adult People Living with HIV in Ethiopia: Systematic Review and Meta-Analysis.

Human immunodeficiency virus remains a global public health problem. Despite efforts to determine the prevalence of non-adherence to ART and its predictors in Ethiopia, various primary studies presented inconsistent findings. Therefore, this review aimed to determine the pooled prevalence of non-adherence to ART and identify its predictors. We have searched PubMed, Google Scholar and Web of Science databases extensively for all available studies. A weighted inverse-variance random-effects model was used to compute the overall non-adherence to ART. The pooled prevalence of non-adherence to ART was 20.68% (95% CI: 17.74, 23.61); I2 = 98.40%; p < 0.001). Educational level of primary school and lower [AOR = 3.5, 95%CI: 1.7, 7.4], taking co-medications [AOR = 0.45, 95%CI: 0.35, 0.59], not using memory aids [AOR = 0.30, 95%CI: 0.13, 0.71], depression [AOR = 2.0, 95%CI: 1.05, 3.79], comorbidity [AOR = 2.12, 95%CI: 1.16, 3.09), under-nutrition [AOR = 2.02, 95%CI: 1.20, 3.43], not believing on ART can control HIV [AOR = 2.31, 95%CI: 1.92, 2.77], lack of access to health facilities [AOR = 3.86, 95%CI: 1.10, 13.51] and taking ART pills uncomfortably while others looking [AOR = 5.21, 95%CI: 2.56, 10.53] were significantly associated with non-adherence to anti-retroviral therapy. The overall pooled prevalence of non-adherence to ART was considerably high in Ethiopia. Educational status, taking co-medications, not using memory aids, depression, comorbidity, under nutrition, not believing on anti-retroviral therapy controls HIV, lack of access to health facilities and taking ART pills uncomfortably were independent predictors of non-adherence to ART in Ethiopia. Therefore, healthcare providers, adherence counselors and supporters should detect non-adherence behaviors and patients' difficulties with ART early, and provide intensive counseling to promote adherence.

Efficacy of the Dapivirine Vaginal Ring Accounting for Imperfect Adherence.

Product adherence is critical to obtaining objective estimates of efficacy of pre-exposure prophylactic interventions against HIV-1 infection. With imperfect adherence, intention-to-treat analyses assess the collective effects of complete, sub-optimal and non-adherence, providing a biased and attenuated estimate of the average causal effect of an intervention. Using data from the MTN-020/ASPIRE phase III trial evaluating HIV-1 efficacy of the dapivirine vaginal ring, we conducted per-protocol, and adherence-adjusted causal inference analyses using principal stratification and marginal structural models. We constructed two adherence cut offs of ≥ 0.9 mg (low cutoff) and > 4.0 mg (high cutoff) that represent drug released from the ring over a 28-day period. The HIV-1 efficacy estimate (95% CI) was 30.8% (3.6%, 50.3%) (P = 0.03) from the per-protocol analysis, and 53.6% (16.5%, 74.3%) (P = 0.01) among the highest predicted adherers from principal stratification analyses using the low cutoff. Marginal structural models produced efficacy estimates (95% CIs) ranging from 48.8 (21.8, 66.4) (P = 0.0019) to 56.5% (32.8%, 71.9%) (P = 0.0002). Application of adherence-adjusted causal inference methods are useful in interpreting HIV-1 efficacy in secondary analyses of PrEP clinical trials.

Antiretroviral therapy non-adherence and its association with psychosocial factors in Nigeria: comparative study of sexual minority and heterosexual men living with HIV.

Sexual minority men (gay, bisexual and other men who have sex with men; SMM) in Nigeria are disproportionately affected by HIV compared to heterosexual men. There is a dearth of research on the correlates of antiretroviral therapy (ART) non-adherence and correlates in both groups. The current study examined the associations of ART non-adherence with sociodemographic and psychosocial characteristics among a sample of Nigerian heterosexual and SMM. Between March and September 2014, we surveyed 120 SMM and 108 heterosexual men receiving ART in Lagos and Abuja, Nigeria. We specified univariate and multivariable linear regression models to examine correlates of ART non-adherence. We found that 50.8% and 29.6% of sexual minority and heterosexual men respectively self-reported ART non-adherence which was significantly associated with psychosocial factors such as stigma, depressive symptoms, and suicidality. Mental health care and psychosocial support should be incorporated into routine HIV care for Nigerian SMM living with HIV.

International Variability of Barriers to Adherence to Immunosuppressive Medication in Adult Heart Transplant Recipients. A Secondary Data Analysis of the BRIGHT Study.

Non-adherence to immunosuppressive medication among transplant patients is associated with poor clinical outcomes and higher economic costs. Barriers to immunosuppressives are a proximal determinant of non-adherence. So far, international variability of barriers to adherence in transplantation has not been studied. As part of the cross-sectional multi-country and multi-center BRIGHT study, barriers to adherence were measured in 1,382 adult heart transplant recipients of 11 countries using the 28-item self-report questionnaire "Identifying Medication Adherence Barriers" (IMAB). Barriers were ranked by their frequency of occurrence for the total sample and by country. Countries were also ranked the by recipients' total number of barriers. Intra-class correlations were calculated at country and center level. The five most frequently mentioned barriers were sleepiness (27.1%), being away from home (25.2%), forgetfulness (24.5%), interruptions to daily routine (23.6%) and being busy (22.8%), fairly consistently across countries. The participants reported on average three barriers, ranging from zero up to 22 barriers. The majority of the variability among reported barriers frequency was situated at the recipient level (94.8%). We found limited international variability in primarily person-level barriers in our study. Understanding of barriers in variable contexts guides intervention development to support adherence to the immunosuppressive regimen in real-world settings.

How to handle a missed or delayed dose of lacosamide in pediatric patients with epilepsy? a mode-informed individual dosing.

This study aims to investigate the effects on the pharmacokinetic (PK) of lacosamide (LCM), and to guide the individual dosing regimens for children and ones with poor medication adherence. Population PK research was performed based on 164 plasma samples of 113 pediatric patients aged from 1.75 to 14.42 years old. The PK characteristic of LCM was developed by a one-compartment model with first-order elimination. The typical value of apparent clearance (CL) and apparent volume of distribution (Vd) was 1.91 L·h-1 and 56.53 L respectively. In the final model, the variability of CL was significantly associated with the body surface area (BSA) and elevated uric acid (UA) level. In contrast, the impact of some prevalent anti-seizure medicines, such as valproic acid, levetiracetam, oxcarbazepine, lamotrigine, and perampanel, and gene polymorphisms of Cytochrome P450 (CYP)2C19, ATP-binding cassette (ABC)B1, and ABCC2 had no clinical significance on the PK parameters of LCM. BSA-based dosing regimen of LCM was provided according to Monte Carlo simulation approach; while the dosage should reduce half in patients with an UA level of more than 400 µmol·L-1 comparing with an UA level of 100 µmol·L-1. Individualize remedial doses of about 0.5- to 1.5-fold of regular doses were recommended in six common scenarios of missed or delayed doses, that depended on the delayed time. In current study, the population PK model of LCM in children with epilepsy was developed successfully. The BSA-based dosing regimen and individualized remedial strategy were recommended to guarantee the precise administration of LCM.

Medication adherence in pediatric kidney transplantation: How to build a bridge over troubled water.

Adhering to the immunosuppressive regimen remains one of the biggest challenges for children and adolescents after kidney transplantation. The first paper on nonadherence, co-authored by Dr. Fine, appeared in Pubmed over 45 years ago. Since then, many clinicians and researchers tried to better understand nonadherence and are looking for effective ways to support young people in implementing the complex medication regimen in their daily lives. As a tribute to Dr. Fine, we conducted a comprehensive review providing an overview of adherence-enhancing interventions in the field of pediatric kidney transplantation, thereby focusing on strategies that not only are effective but can also be embedded in daily clinical practice successfully and sustainably. This overview is preceded by a discussion about how to find out who is in need of supportive interventions. We will also argue that interventions should already start before pediatric kidney transplantation and discuss how to decide whether or not a young patient with nonadherence-induced graft loss should undergo retransplantation. We hope this comprehensive overview will rekindle the hope that we can finally turn the tide and beat one of pediatric kidney transplantation's main enemies.

Medication non-adherence and predictor factors among adult asthmatic patients in Ethiopia: a systematic review and meta-analysis.

OBJECTIVE: A pronounced burden is evident in individuals with asthma, with approximately half of them not adhering to their prescribed medication. Therefore, this study aimed to assess the pooled prevalence of anti-asthma medications non-adherence in Ethiopia. DATA SOURCES: A comprehensive search was conducted across multiple electronic databases including PubMed, Africa Index Medicus, Science Direct, Hinari, and a search engine, Google Scholar from October 5 to 20, 2023. In addition, digital research repositories from Addis Ababa and Bahir Dar University were accessed. DATA SELECTION: The eligibility criteria was employed to screen studies after uploading search results to EndNote software to remove duplicates first. Then, two investigators, CT and BBT, independently assessed titles, abstracts, and the full text of all retrieved references to identify potentially eligible studies. RESULT: This meta-analysis, which was conducted in Ethiopia, and included 11 full-text articles, revealed a pooled asthma medication non-adherence level of 51.20% (95% CI 35.20%, 67.20%) with substantial heterogeneity (I2 = 99.08%). The review has also identified factors predicting non-adherence among asthmatic patients: free (health service) (AOR: 0.31, 95% CI 0.18-0.54), poor knowledge (AOR: 2.85, 95% CI 1.61-5.05), absence of formal education (AOR: 3.01, 95% CI 1.72-5.25), history of previous ADR (AOR: 8.57, 95% CI 1.12-65.3), and the presence of Co- morbidity(AOR: 3.28, 95% CI 2.014-5.68), had shown association with asthma medication non-adherence. CONCLUSION: Asthma medication non-adherence is notably high in Ethiopia. Addressing medication non-adherence requires a comprehensive approach, including clear communication between healthcare providers, patient education, and addressing financial barriers to ensure better adherence in asthma patients.

Acute kidney injury in lamotrigine-induced DRESS syndrome.

We present a case of lamotrigine-triggered DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome with acute kidney injury stage 3. A 17-year-old girl with known epilepsy treated with lamotrigine presented with acute kidney injury as well as skin eruption, fever, and apathy. Extended diagnostics, considering infectious and autoimmune diseases, remained unremarkable. Lamotrigine blood levels were within the target range. Kidney biopsy showed acute interstitial nephritis with tubular necrosis. Methylprednisolone pulse therapy led to an improvement in kidney function; skin eruption and neurological symptoms resolved. During the hospital stay, the girl admitted to inconsistent and variable intake of lamotrigine, occasionally resulting in notable overdosing. This report demonstrates that acute kidney injury in lamotrigine-induced DRESS syndrome is an acute interstitial nephritis with tubular necrosis, an aspect that has not been deeply characterized so far. Additionally, we aim to elevate awareness towards non-adherence as cause of disease, especially among the adolescent population.

Non-adherence and non-persistence with antiretroviral treatment in Belgium: A real-world evaluation using a pharmacy database, 2018-2021.

PURPOSE: To evaluate the real-world rates of non-adherence and non-persistence to antiretroviral therapy (ART) among treatment-naïve adult patients with HIV after a 12-month follow-up period in Belgium. METHODS: A retrospective analysis of longitudinal pharmacy claims was conducted using the Pharmanet database from January 1, 2018, to December 31, 2021. Non-adherence was assessed over 12 months and reported as the proportion of days covered below the 80% threshold. Non-persistence was defined as the first 90-day gap in treatment between the two types of ART dispensed. Poisson regression with robust standard error and Cox proportional hazard models were used to assess the factors associated with non-adherence and non-persistence, respectively. RESULTS: Overall, 2999 patients were initiated on ART between 2018 and 2021. After a 12-month follow-up, the proportions of non-adherence and non-persistence were 35.6% and 15.9%, respectively in 2018, and decreased to 18.7% and 6.8%, respectively in 2021. Non-adherence was higher among women, Brussels residents, and those receiving multiple-tablet regimens (MTRs). Similarly, the prevalence of non-persistence was higher among women and MTR recipients. CONCLUSION: Among treatment-naïve adults with HIV in Belgium, non-adherence, and non-persistence to ART showed improvement over the study period but remained at high levels. Disparities were observed by sex and between geographical regions. Prioritizing strategies targeting women in Brussels and facilitating the transition from MTRs to single-tablet regimens should be emphasized optimize adherence to ART in Belgium.

Determination of a cut-off COmprehensive Score for financial Toxicity (COST) for identifying cost-related treatment nonadherence and impaired health-related quality of life among Chinese patients with cancer.

PURPOSE: This study aimed to determine a cut-off for the simplified Chinese version of the COmprehensive Score for financial Toxicity (COST) that could identify cost-related treatment nonadherence among Chinese patients with cancer. The study also sought to validate this cut-off score by using it to assess impaired health-related quality of life (HRQoL) in the same population. METHODS: A secondary analysis was conducted using data from a cross-sectional survey of 1208 Chinese patients with cancer who were recruited from 12 hospitals in six cities across three provinces of the Chinese mainland. Sociodemographic information and data on financial toxicity (FT), cost-related treatment nonadherence, and HRQoL were used in the analysis. Receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off for the simplified Chinese version of the COST. RESULTS: The ROC analysis identified a COST cut-off of 18.5 for identifying cost-related treatment nonadherence, yielding a sensitivity of 76.5% and specificity of 71.4%. In the validation study, this cut-off score yielded a sensitivity of 64.2% and a specificity of 67.1% for identifying impaired HRQoL. CONCLUSION: Early and dynamic assessment of cancer-related FT in routine clinical practice may play a crucial role in the early identification and management of FT. Accordingly, a COST cut-off of 18.5 was identified to indicate cost-related treatment nonadherence and impaired HRQoL in a population of patients with cancer from the Chinese mainland. This finding may facilitate the implementation of universal FT screening among patients with cancer in specific settings such as the Chinese mainland.

Understanding and Quantifying Network Robustness to Stochastic Inputs.

A variety of biomedical systems are modeled by networks of deterministic differential equations with stochastic inputs. In some cases, the network output is remarkably constant despite a randomly fluctuating input. In the context of biochemistry and cell biology, chemical reaction networks and multistage processes with this property are called robust. Similarly, the notion of a forgiving drug in pharmacology is a medication that maintains therapeutic effect despite lapses in patient adherence to the prescribed regimen. What makes a network robust to stochastic noise? This question is challenging due to the many network parameters (size, topology, rate constants) and many types of noisy inputs. In this paper, we propose a summary statistic to describe the robustness of a network of linear differential equations (i.e. a first-order mass-action system). This statistic is the variance of a certain random walk passage time on the network. This statistic can be quickly computed on a modern computer, even for complex networks with thousands of nodes. Furthermore, we use this statistic to prove theorems about how certain network motifs increase robustness. Importantly, our analysis provides intuition for why a network is or is not robust to noise. We illustrate our results on thousands of randomly generated networks with a variety of stochastic inputs.

Antipsychotic medication non-adherence and factors associated among patients with schizophrenia in eastern Ethiopia.

BACKGROUND: Given that antipsychotic medication is a cornerstone for treating and preventing relapse in people with schizophrenia, non-adherence has been indicated as a big challenge. This study aimed to assess antipsychotic medication non-adherence and factors associated among patients with schizophrenia in eastern Ethiopia. METHODS: We conducted an institution-based cross-sectional study in two public hospitals in Eastern Ethiopia from December 1, 2022, to January 31, 2023. Antipsychotic medication adherence was assessed using MOrisky medication adherence rating scale questionnaire, and insight was measured using the self-report insight scale for Psychosis (ISP). Multiple stepwise logistic regression models with Adjusted Odds Ratio (AOR) and 95% confidence interval (CI) were applied to identify the factors. Statistical significance was considered at p-value ≤ 0.05. RESULTS: We found that 44.57% of patients with schizophrenia experienced non-adherence to their antipsychotic medication. Being single (AOR = 2.48, 95% confidence interval [CI]:1.71, 3.58), alcohol users (AOR = 2.00, 95% confidence interval [CI]:1.46, 2.72), Khat chewers (AOR = 2.84, 95% confidence interval [CI]; 2.06, 3.90) and having no insight to their illness (AOR = 2.1, 95% confidence interval [CI]:1.52, 2.90) were more likely to be non-adherent to their antipsychotic medications. CONCLUSIONS: Our study revealed that antipsychotic medication non-adherence was high among individuals suffering from schizophrenia and that it was influenced by various factors such as single marital status, alcohol usage, Khat chewing, and having no understanding of their condition. As a result, comprehensive intervention methods should be developed to address the factors associated with psychotropic medication non-adherence among patients. Healthcare professionals should pay attention to these aspects and consider developing specific strategies to promote adherence to medications while treating individuals with schizophrenia.