ERS Statement on pediatric long term noninvasive respiratory support

Long term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced pediatric multidisciplinary team. This Statement written by experts in the field of pediatric long term CPAP/NIV aims to emphasize on the most recent scientific input and should open up to new perspectives and research areas.

Mediterranean diet in axial spondyloarthritis: an observational study in an Italian monocentric cohort

Background Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA. Methods We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score). Results A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls (p = 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1, p = 0.014), age (per 10-year increase OR 1.05, 1.02–1.68, p = 0.007), and BMI (OR 0.77, 0.63–0.9, p = 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls (p = 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3, p = 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement. Conclusions Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are less prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement. Study registration Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

Love, sex, drugs and women’s sub-optimal adherence to MDR-TB treatment in South Africa: Opportunities for enhanced health education

Objective: Rising incidence of acquired multidrug-resistant tuberculosis (MDR-TB) in South Africa suggests low knowledge and implementation of infection prevention and control strategies in household and congregate settings. This study contributes to the under-researched area of non-biomedical responses to sub-adherence to treatment. Design: The study utilises a quasi-ethnographic qualitative case study of 10 women aged 18 to 34 years to understand their treatment adherence behaviours through the lens of their sex, gender, age, cultural beliefs and socio-economic status. Setting: This study investigated reasons for young women’s sub-optimal adherence to treatment for acquired MDR-TB in eThekwini Metro, KwaZulu-Natal province, South Africa, which records high burdens of tuberculosis (TB), MDR-TB and HIV. Methods: Primary data were collected from 20 participants who were selected through criterion, purposive and snowball sampling. Data were gathered through focus group discussions with women being treated for transmitted MDR-TB and key informant interviews with their family members, health workers and KwaZulu-Natal Provincial Department of Health personnel. Results: Anti-MDR-TB treatment affects women’s sexuality, intimate relationships, family planning intentions and reproductive health. Some vulnerable women struggle to persevere on noxious and lengthy treatment regimes that affect their reproductive and psychological health. Women may skip doses or abandon treatment when high pill burdens and adverse events make intimate and sexual relations with male partners, on whom they may depend for their livelihoods, difficult. Conclusion: It is important to consider the effects of lengthy treatment on young people’s social and sexual lives and self-esteem when (re)designing MDR-TB counselling approaches. This paper advances an evidence-based treatment education and counselling strategy to contribute to improving MDR-TB treatment adherence and success.

Feasibility of implementing a same-day electronic screening tool for clinical assessment to measure patient-reported outcomes for eliciting actionable information on adherence to HIV medication and related factors in a busy Canadian urban HIV clinic

Background: An optimal adherence to antiretroviral therapy (ART) is fundamental for suppression of HIV viral load and favourable treatment outcomes. Patient-reported outcomes (PROs) are effective tools for improving patient–provider communication and focusing providers’ awareness on current health problems. The objectives of this analysis were (1) to determine the feasibility of implementing an electronic screening tool to measure PROs in a Canadian HIV clinic to obtain information on ART adherence and related factors and (2) to determine the factors related to sub-optimal adherence. Methods: This implementation research with a convenience sample of 600 people living with HIV (PLWH) was conducted in a busy, academic, urban HIV clinic in Toronto, Canada. PLWH were approached to participate in PRO assessments just prior to their in-clinic appointments, including health-related domains such as mental health, housing, nutrition, financial stress and medication adherence, and responses were summarized on a single sheet available for providers to review. Feasibility of implementing PROs was assessed by quantifying response rate, completion rate, time taken and participation rate. Medication adherence was elicited by self-report of the percentage of prescribed HIV medications taken in the last month. Unadjusted and adjusted odds ratios were estimated from logistic regression models to identify factors associated with adherence of <95%. Results: Of the 748 PLWH invited to participate, 692 (participation rate: 92.5%) completed the PRO assessments as standard of care in clinic. Of these, 600 consented to the use of their PRO results for research and were included in this analysis. The average response rate to the ART-related questions was 96.8% and mean completion rate was 95.5%. The median time taken to complete the assessment was 12.0 (IQR = 8.4–17.3) min, adjusted 8.7 (IQR = 7.2–10.8) min. 445 (74.9%) of participants were male, and 153 (26.2%) reported dissatisfaction with ART. 105 (19.7%) of the PLWH reported ART adherence of <95%. Multivariable logistic regression identified the following risk factors for sub-optimal adherence: dissatisfaction with ART (OR = 2.30, 95% CI 1.38–3.83), not having a family doctor or not visiting a family doctor in last year (OR = 1.69, 95% CI 1.02–2.79). Conclusion: Collecting self-reported health information from PLWH through PROs in a busy urban clinic was feasible and can provide relevant information to healthcare providers on issues related to adherence. This has a potential to help in individualizing ambulatory care.

Multilevel of Factors Affected Optimal Adherence to Antiretroviral Therapy and Viral Suppression Amongst HIV-infected Prisoners in South Ethiopia: A Prospective Cohort Study

ObjectivesMaintaining optimal adherence and viral suppression in people living with HIV (PLWHA) is essential to ensure both preventative and therapeutic benefits of antiretroviral therapy (ART). Prisoners bear a particularly high burden of HIV infection and are highly likely to transmit to others during and after incarceration. However, the level of treatment adherence and viral suppression in incarcerated populations in low-income countries is unknown. This study aimed to determine the prevalence of non-adherence and viral failure, and contributing factors amongst prisoners in South Ethiopia. MethodsA prospective cohort study was conducted between June 1, 2019 and May 31, 2020 to compare the level of adherence and viral suppression between incarcerated and non-incarcerated PLWHA. The study involved 74 inmates living with HIV (ILWHA) and 296 non-incarcerated PLWHA. Background information (including sociodemographic, socioeconomic, psychosocial, behavioural, and incarceration related characteristics) was collected using a structured questionnaire. Adherence was determined based on the participants’ self-report and pharmacy refill records. Plasma viral load measurements undertaken within the study period were prospectively extracted to determine viral suppression. Univariate and multivariate regression models were used to analyse data. ResultsWhile prisoners had a significantly higher pharmacy refill adherence compared to non-incarcerated PLWHA (89% vs 75%), they had a slightly lower dose adherence (81% vs 83%). The prevalence of viral failure (VF) was also slightly higher (6%) in ILWHA compared to non-incarcerated PLWHA (4.4%). The overall dose non-adherence (NA) was significantly associated with missing ART appointments, level of satisfaction with ART services, patient’s ability to comply with a specified medication schedule and types of methods used to monitor the schedule. In ILWHA specifically, accessing ART services from a hospital compared to a health centre, an inability to always attend clinic appointments, experience of depression and a lack of social support predicted NA. VF was significantly higher in males, people of age 31to 35 years and in those who experienced social stigma, regardless of their incarceration status. ConclusionsThis study revealed that HIV-infected prisoners in South Ethiopia were more likely to be non-adherent to ART doses and to develop viral failure compared to their non-incarcerated counterparts. A multitude of factors were found to be responsible for this requiring multilevel intervention strategies focusing on the specific needs of prisoners.

Association between hyperkalemia, RAASi non-adherence and outcomes in chronic kidney disease

Background Hyperkalemia is relatively frequent in CKD patients treated with renin-angiotensin-aldosterone-system inhibitors (RAASi). Aim The aim of the present study was to estimate the increased risk of cardiovascular events and mortality due to sub-optimal adherence to RAASi in CKD patients with hyperkalemia. Methods An observational retrospective cohort study was conducted, based on administrative and laboratory databases of five Local Health Units. Adult patients discharged from the hospital with a diagnosis of CKD, who were prescribed RAASi between January 2010 and December 2017, were included. We evaluated the appearance of documented episodes of hyperkalemia, RAASi therapy adherence and the effects of these two variables on cardiovascular events, death and dialysis inception for study patients. Results Of the 9241 selected patients, 4451 met all the criteria for study inclusion. Among them, 1071 had at least one documented episode of hyperkalemia, while 3380 did not. After propensity score matching based on several variables we obtained 2 groups of patients. The appearance of hyperkalemia caused treatment discontinuation in 21.8% of patients previously on RAASi therapy, and sub-optimal adherence (proportion of days covered < 80%) in 33.6% of them. Non-adherence to RAASi therapy among hyperkalemia patients was associated with a higher risk of cardiovascular events (hazard ratio [HR] 1.45, confidence interval [CI] 1.02–2.08; p < 0.05). Moreover, in non-adherent hyperkalemia patients, the risk of death increased by 126% (HR 2.26, CI 1.62–3.15; p < 0.001) compared with adherent patients. Conclusions In a large cohort of CKD patients treated with RAASi, we observed that following hyperkalemia onset, non-adherence to RAASi medication can result in an increased risk of cardiovascular events and death. Graphical abstract

Retrospective real-world comparison of clinical and economic burden between first-generation and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).

e19030 Background: TKIs are the standard of care for the treatment of chronic phase CML under National Comprehensive Cancer Network (NCCN) guidelines. Imatinib is recommended as a first-generation TKI (1GTKI), and bosutinib, dasatinib, nilotinib, and ponatinib are recommended as second-generation TKIs (2GTKIs). TKIs are associated with high healthcare resource utilization (HRU) and costs, although literature is limited comparing 1GTKI and 2GTKIs in a U.S. population. Methods: Using the Veteran’s Health Administration (VHA) database between April 1, 2013 and March 31, 2018, the study included patients aged ≥18 years with ≥1 medical claim for CML and ≥1 prescription claim for a TKI on or after the initial CML diagnosis date during the identification period (October 1, 2014 to September 30, 2017); the first TKI prescription claim was defined as the index date. Inverse probability of treatment weighting (IPTW) minimized potential confounding; included variables were age, race, Quan-Charlson Comorbidity Index (CCI) score, and CHA2DS2-VASc Score. Medication possession ratio (MPR) assessed adherence to index TKI; optimal adherence was defined as MPR ≥80%. Results: 944 patients were included: 78.9% on 1GTKI and 21.1% on 2GTKI. Mean age was 62.21 years (SD:18.8); 77.2% were white. At baselinetients on 1GTKI had a higher comorbidity burden than 2GTKIs: COPD (19.7% vs. 8%; p < 0.01), anemia (17.7% vs. 11.1%; p = 0.02), GI symptoms (28.5% vs. 18.6%; p < 0.01), cardiac dysrhythmias (15.6% vs. 7.5%; p < 0.01), coronary artery disease (26.3% vs. 13.6%; p < 0.01), hypertension (55.7% vs. 43.2%; p < 0.01) and CHA2DS2-VASc Score (2.2 vs 1.6; p < 0.01). Optimal adherence was higher with 1GTKI (69.6% vs. 62.2%; p = 0.04), although this was not statistically significant when mean MPR was compared. During follow-up, no difference between 1GTKI and 2GTKIs patients occurred with cardiac-related risk factors or CHA2DS2-VASc Score. Compared to 1GTKI, 2GTKIs had lower medical (inpatient and outpatient) costs ($3,162 vs. $3,906; p = 0.04) but higher all-cause pharmacy cost ($7,214 vs. $3,895; p < 0.01) due to imatinib becoming a generic drug during the study period. CML-related ($2,260 vs. $1,640, p < 0.01) and cardiac-related medical costs ($1,365 vs. $665, p < 0.01) were significantly higher in 1GTKI vs. 2GTKIs patients. Conclusions: Adherence to TKI therapy was suboptimal for both 1GTKI and 2GTKIs. 2GTKIs incurred lower medical cost in comparison to 1GTKI. Differences in total all-cause cost was primarily driven by pharmacy cost of TKIs. These results show that, beyond the cost of the TKI, using a 2GTKIs in the first-line can lead to cost offsets when compared to imatinib.

A Machine Learning Approach for Identifying Children at Risk of Suboptimal Adherence to Growth Hormone Therapy

Background: Suboptimal adherence to recombinant human growth hormone (r-hGH) treatment can lead to suboptimal clinical outcomes. Being able to identify children who are at risk of suboptimal adherence in the near future, and take adequate measures to support adherence, may maximize clinical outcomes. Our aim was to develop a model based on data from the first 3 months of treatment to identify potential indicators of suboptimal adherence and predict adherence over the following 9 months using a machine learning approach. Methods: We assessed adherence to r-hGH treatment in children with growth disorders in their first 12 months of treatment using a connected autoinjector and e-device (easypod™), which automatically transmits adherence data via an online portal (easypod™ connect). We selected children who started the use of the device before 18 years of age and who transmitted their injection data for at least 12 months. Adherence (mg injected/mg prescribed) between 4-12 months (outcome) was categorized as optimal (≥85%) versus suboptimal (&lt;85%). In addition to adherence over the first 3 months, comfort settings (needle speed, injection depth, injection speed, injection time), number of transmissions, number of dose changes, age at start and sex were used as potential indicators of suboptimal adherence. Several machine learning models were optimized on a class-balanced training dataset using a 5-fold cross-validation scheme. On the best performing model, machine learning interpretation techniques and chi-squared statistical tests were applied to extract the statistically significant indicators of suboptimal and optimal adherence. Results: Anonymized data were available for 10,943 children. The optimal prediction performances were achieved with the random forest algorithm. The mean adherence and the adherence standard deviation over the first 3 months were the two most important features for predicting adherence in the following 9 months. Not using the system’s features (e.g. not transmitting data often and not changing some of the comfort settings, such as the needle speed setting), as well as starting treatment at an older age were significantly associated with an increased risk of suboptimal adherence (p&lt;0.001). When tested on first-time seen data following the same class distribution as the original data, the model achieved a sensitivity of 80% and a specificity of 81%. Conclusions: We developed a model predicting whether a child’s adherence in the following 9 months will be below or above the optimal threshold (85%) based on early data from the first 3 months of treatment and we identified the indicators of suboptimal adherence. These results can be used to identify children needing additional medical or other support to reach optimal adherence and therefore optimal clinical outcomes.

Sub-Optimal Adherence With Daily Growth Hormones Increases With Each Year of Treatment in a US Commercial Claims Database

Introduction and Objective: Pediatric growth hormone deficiency (pGHD) occurs in approximately 1 in 4,000 children. The main manifestation is short stature managed with daily injections of somatropin, a recombinant human growth hormone (r-hGH). Prior research has shown that children with good adherence with r-hGH have significantly greater linear growth compared to those with sub-optimal adherence. While previous studies have found sub-optimal adherence with daily r-hGH injectables among children with pGHD, to date, r-hGH adherence has not been studied among large, usual-care populations using validated measurements of adherence. We describe adherence to somatropin treatment over 4 years in a population-based study. Materials and Methods: A retrospective cohort analysis of commercially insured patients ≥3 and &lt;16 years, diagnosed with pGHD, newly treated with somatropin from 01 January 2002 through 31 December 2019 (study time period) was conducted using Optum De-identified Clinformatics Data Mart database. Index date was defined as the first prescription for somatropin between 01 July 2002 to 30 September 2019. Four patient cohorts were identified (12, 24, 36, and 48 months of post-index continuous enrollment). The demographic and clinical profiles of children with pGHD treated with daily injections of somatropin who have good adherence and those with sub-optimal adherence were characterized. Good adherence was defined as medication possession ratio (MPR) of ≥ 80%, sub-optimal adherence as MPR &lt;80%. Logistic regression models will evaluate the relationship between demographic characteristics (age, gender, race/ethnicity) and adherence (good vs. sub-optimal). Results: Patient characteristics were similar across each cohort; in the 12-month cohort (n=3091), mean age was 11.34 ±2.89 years, 75.9% were male, 70.9% white, 9.4% Hispanic, 3.6% Asian, and 3.1% black. At 48 months, 1193 (38.6%) of the 12-month cohort remained for follow-up. At 12 months, 80.1% had good adherence and mean (95% CI) MPR was 0.89 (0.88-0.89) while mean (95% CI) MPR at 48 months was 0.82 (0.81-0.83). The proportion with good adherence at months 24, 36, and 48 were 70.2%, 65.6%, and 64.0%, respectively. Adherence was not associated with age or gender. Blacks and Hispanics consistently exhibited lower adherence. At 12 months, good adherence was observed among 85.7% of Asians, 80.0% of whites, 77.2% of Hispanics, and 76.0% of blacks; at 48 months, good adherence was observed among 73.9% of Asians, 65.4% of whites, 56.8% of blacks, and 55.2% of Hispanics. Logistic regression model results will be provided. Conclusion: Although the majority of children with pGHD demonstrated good adherence with a daily r-hGH regimen, sub-optimal adherence increases with treatment duration and is higher among black and Hispanic children. Strategies that facilitate good adherence to r-hGH may support improved clinical outcomes.