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.

Meta-analysis of placebo-arm dropouts in osteoporosis randomized-controlled trials and implications for nocebo-associated discontinuation of anti-osteoporotic drugs in clinical practice.

Dropout from placebo arms in randomized-controlled trials is a surrogate for nocebo responses, resulting from patients' negative expectations to treatment. Among 16,460 placebo-treated patients in oral anti-osteoporotic drug trials, nocebo dropouts were 8% on average, being higher in older patients. This implies that nocebo may contribute to the osteoporosis treatment gap in clinical practice. PURPOSE: Osteoporosis is a common disease requiring long-term treatment. Despite the availability of effective anti-osteoporotic drugs, adherence to treatment is low. Nocebo, a behavior mostly related to the negative expectations to a certain treatment, decreases adherence and negatively affects treatment outcomes and health-related care costs in chronic diseases. Since in double-blind placebo-controlled randomized trials any unfavorable outcome leading to discontinuation in placebo arms is considered as nocebo, we aimed to investigate the size of nocebo response in patients participating in osteoporosis trials. METHODS: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for dropouts due to reported adverse events in the placebo arms (nocebo dropouts) in all double-blind trials investigating anti-osteoporotic drugs published between January 1993 and March 2022. Only data on bisphosphonates and selective estrogen receptor modulators (SERMs) were analyzed (Prospero registration number CRD42020212843). RESULTS: Data from 44 trials were extracted. In 16,460 placebo-treated patients, the pooled nocebo-dropout was 8% both for bisphosphonates (average: 0.08; range 0.01-0.27; 95%CI 0.06-0.10) and SERMs (average: 0.08; range 0.03-0.15; 95%CI 0.05-0.13). Nocebo-dropouts were higher in bisphosphonate trials enrolling individuals ≥ 65 years (11%) (n = 18) compared to trials enrolling younger individuals (6%) (n = 18) (average: 0.11; 95%CI 0.08-0.13 vs. average: 0.06; 95%CI 0.05-0.08, respectively, p = 0.001). Participants' sex, dosing-intervals, publication year, or severity of osteoporosis had no impact on the nocebo-dropouts. CONCLUSION: Almost 1 in 10 osteoporosis patients receiving placebo in trials of bisphosphonates and SERMs experiences AEs leading to dropout, implying that nocebo contributes to treatment-discontinuation in clinical practice. Efforts to identify and minimize nocebo, especially in older patients, are warranted.

Predictors of financial toxicity and its associations with health-related quality of life and treatment non-adherence in Turkish cancer patients.

PURPOSE: This study aims to determine the financial toxicity (FT) level in cancer patients, identify the risk factors associated with this level, and reveal the effect of this level on patient outcomes (health-related quality of life (HRQoL) and treatment non-adherence). METHODS: The data of 316 cancer patients, who were receiving inpatient treatment in an oncology hospital affiliated to a public university in Ankara, Turkey, were ≥ 18 years old, and were receiving chemotherapy for at least 3 months, were evaluated. The data were collected through a face-to-face interview. FT was measured with the COmprehensive Score for financial Toxicity (COST) Measure (v2), HRQoL was measured with the Functional Assessment of Cancer Therapy-General (FACT-G) Scale (v4), and treatment adherence was measured using a questionnaire created by conducting a literature review. RESULTS: Patients were found to experience FT above the moderate level (mean ± SD, 21.85 ± 12.02; median value, 24.0). Younger age, being married, low education level, low monthly household income, and receiving social/economic support for treatment were revealed to be the determinants of high FT. Moreover, as the FT score decreased (as the FT level felt increased), the HRQoL was observed to decrease, and treatment non-adherence increased. CONCLUSION: The results indicate that FT problem is also valid for cancer patients in Turkey despite the system of general health insurance. The FT was found to result from socio-economic characteristics rather than the disease and treatment-related characteristics. The significant associations revealed between FT and patient outcomes emphasize the importance of reducing the FT in cancer patients.

Non-adherence in difficult-to-treat rheumatoid arthritis from the perspectives of patients and rheumatologists: a concept mapping study.

OBJECTIVES: Treatment non-adherence is more frequent among difficult-to-treat (D2T) than among non-D2T RA patients. Perceptions of non-adherence may differ. We aimed to thematically structure and prioritize barriers to (i.e. causes and reasons for non-adherence) and facilitators of optimal adherence from the patients' and rheumatologists' perspectives. METHODS: Patients' perceptions were identified in semi-structured in-depth interviews. Experts selected representative statements regarding 40 barriers and 40 facilitators. Twenty D2T and 20 non-D2T RA patients sorted these statements during two card-sorting tasks: first, by order of content similarity and, second, content applicability. Additionally, 20 rheumatologists sorted the statements by order of content applicability to the general RA population. The similarity sorting was used as input for hierarchical cluster analysis. The applicability sorting was analysed using descriptive statistics, prioritized and the results compared between D2T RA patients, non-D2T RA patients and rheumatologists. RESULTS: Nine clusters of barriers were identified, related to the healthcare system, treatment safety/efficacy, treatment regimen and patient behaviour. D2T RA patients prioritized adverse events and doubts about effectiveness as the most important barriers. Doubts about effectiveness were more important to D2T than to non-D2T RA patients (P = 0.02). Seven clusters of facilitators were identified, related to the healthcare system and directly to the patient. All RA patients and rheumatologists prioritized a good relationship with the healthcare professional and treatment information as the most helpful facilitators. CONCLUSIONS: D2T RA patients, non-D2T RA patients and rheumatologists prioritized perceptions of non-adherence largely similarly. The structured overviews of barriers and facilitators provided in this study may guide improvement of adherence.

Bipolar I disorder: a qualitative study of the viewpoints of the family members of patients on the nature of the disorder and pharmacological treatment non-adherence.

BACKGROUND: Bipolar disorder is a common psychiatric disorder with a massive psychological and social burden. Research indicates that treatment adherence is not good in these patients. The families' knowledge about the disorder is fundamental for managing their patients' disorder. The purpose of the present study was to investigate the knowledge of the family members of a sample of Iranian patients with bipolar I disorder (BD-I) and to explore the potential reasons for treatment non-adherence. METHODS: This study was conducted by qualitative content analysis. In-depth interviews were held and open-coding inductive analysis was performed. A thematic content analysis was used for the qualitative data analysis. RESULTS: The viewpoints of the family members of the patients were categorized in five themes, including knowledge about the disorder, information about the medications, information about the treatment and the respective role of the family, reasons for pharmacological treatment non-adherence, and strategies applied by families to enhance treatment adherence in the patients. The research findings showed that the family members did not have enough information about the nature of BD-I, which they attributed to their lack of training on the disorder. The families did not know what caused the recurrence of the disorder and did not have sufficient knowledge about its prescribed medications and treatments. Also, most families did not know about the etiology of the disorder. CONCLUSION: The lack of knowledge among the family members of patients with BD-I can have a significant impact on relapse and treatment non-adherence. These issues need to be further emphasized in the training of patients' families. The present findings can be used to re-design the guidelines and protocols in a way to improve treatment adherence and avoid the relapse of BD-I symptoms.

Pharmacist-led intervention in treatment non-adherence and associated direct costs of management among ambulatory patients with type 2 diabetes in southwestern Nigeria.

BACKGROUND: Non-adherence to recommended therapy remains a challenge to achieving optimal clinical outcome with resultant economic implications. OBJECTIVE: To evaluate the effect of a pharmacist-led intervention on treatment non-adherence and direct costs of management among patients with type 2 diabetes (T2D). METHOD: A quasi-experimental study among 201-patients with T2D recruited from two-tertiary healthcare facilities in southwestern Nigeria using semi-structured interview. Patients were assigned into control (HbA1c < 7%, n = 95) and intervention (HbA1c ≥ 7%, n = 106) groups. Baseline questionnaire comprised modified 4-item Medication Adherence Questions (MAQ), Perceived Dietary Adherence Questionnaire (PDAQ) and International Physical Activity Questionnaire, to assess participants' adherence to medications, diet and physical activity, respectively. Post-baseline, participants were followed-up for 6-month with patient-specific educational intervention provided to resolve adherence discrepancies in the intervention group only, while control group continued to receive usual care. Subsequently, direct costs of management for 6-month pre-baseline and 6-month post-baseline were estimated for both groups. Data were summarized using descriptive statistics. Chi-square, McNemar and paired t-test were used to evaluate categorical and continuous variables at p < 0.05. RESULTS: Mean age was 62.9 ± 11.6 years, and 160(79.6%) were females. Glycated haemoglobin (HbA1c) was 6.1 ± 0.6% (baseline) and 6.1 ± 0.8% at 6-month post-baseline (p = 0.094) for control group, and 8.7 ± 1.5% (baseline) versus 7.8 ± 2.0% (6-month), p < 0.001, for the intervention. Post-baseline, response to MAQ items 1 (p = 0.017) and 2 (p < 0.001) improved significantly for the intervention. PDAQ score increased significantly from 51.8 ± 8.8 at baseline to 56.5 ± 3.9 at 6-month (p < 0.001) for intervention, and from 56.3 ± 4.0 to 56.5 ± 3.9 (p = 0.094) for the control group. Physical activity increased from 775.2 ± 700.5 Metabolic Equivalent Task (MET) to 829.3 ± 695.5MET(p < 0.001) and from 901.4 ± 743.5MET to 911.7 ± 752.6MET (p = 0.327) for intervention and control groups, respectively. Direct costs of management per patient increased from USD 327.3 ± 114.4 to USD 333.0 ± 118.4 (p = 0.449) for the intervention, while it decreased from USD 290.1 ± 116.97 to USD289.1 ± 120.0 (p = 0.89) for control group, at baseline and 6-month post-baseline, respectively. CONCLUSION: Pharmacist-led intervention enhanced adherence to recommended medications, diet and physical activity among the intervention patients, with a corresponding significant improvement in glycaemic outcome and an insignificant increase in direct costs of management. There is a need for active engagement of pharmacists in management of patients with diabetes in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04712916 . Retrospectively-registered.

Associations Among Depressive Symptoms, Wellness, Patient Involvement, Provider Cultural Competency, and Treatment Nonadherence: A Pilot Study Among Community Patients Seen at a University Medical Center.

Treatment nonadherence is a pernicious problem associated with increasing rates of chronic diseases, escalating healthcare costs, and rising mortality in some patients. Although researchers have suggested numerous factors related to treatment nonadherence, several understudied aspects warrant attention, such as primary-care settings, provider cultural competence, and patient involvement. Adding to the research base, the present pilot study examined 88 primarily Black American and White American community patients from a large university medical center in the southern part of the United States. The study explored two research questions: (a) To what extent are there associations among depressive symptoms, wellness, patient involvement, cultural competency, and treatment nonadherence in a racially diverse community patient population? And (b) to what extent do the study exploratory variables and background characteristics predict treatment nonadherence, both separately and jointly? Depressive symptoms, the patient's perception of a provider's cultural competence, and marital/partnered status were found to be statistically significantly associated with treatment nonadherence, but not entirely in the directions expected.

Nocebo-associated treatment discontinuation with subcutaneous anti-osteoporotic drugs. A systematic review and meta-analysis of placebo-arm dropouts in randomized-controlled trials.

OBJECTIVE: Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs. STUDY DESIGN: We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023. MAIN OUTCOME MEASURE: Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts"). RESULTS: Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046). CONCLUSION: Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843.

Factors Associated with Non-Adherence to Tuberculosis Preventive Treatment among Adult Contacts of Pulmonary Tuberculosis Cases with Latent Tuberculosis Infection in Catalonia, Spain, in 2019-2021.

The aim of this study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection for new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables; a p < 0.05 was considered statistically significant. Multiple logistic regression analysis was used to detect the independent factors associated with TB preventive treatment non-adherence; a p < 0.05 was considered statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: "exposure at school or workplace" (aOR = 3.34), "exposure to an index case without laboratory confirmation of TB" (aOR = 2.07), "immigrant contact" (aOR = 1.81), "male gender" (aOR = 1.75) and "exposure duration < 6 h per week or sporadic" (aOR = 1.60. By contrast, the factor "short-term TB preventive treatment regimen" (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Study of Adherence Level and the Relationship Between Treatment Adherence, and Superstitious Thinking Related to Health Issues Among Chronic Disease Patients in Southern Jordan: Cross-Sectional Study.

Background: For disease management, numerous drugs are prescribed. However, long-term treatment adherence is still unsatisfactory. Culture influences beliefs regarding medication, particularly irrational ideas that affect treatment adherence. The Middle East, notably Jordan, is affected by a lack of awareness of these attitudes with regard to treatment adherence. Objective: Investigating the adherence level among patients with chronic diseases in southern Jordan. To determine whether certain demographic traits, different disease factors, and superstitions have any impact on treatment adherence. Patients and Methods: A cross-sectional study that assessed treatment adherence and superstitious thinking-related health issues were conducted among chronic disease patients who had reviewed intrinsic medicine clinics at the Karak governmental hospital. Results: For 314 participants, treatment adherence was categorized into three levels low-adherent patients made up 27.7% highly-adherent patients made up 49.4%, and the remaining adhered at a medium level. Treatment non-adherence was more common in the elderly and female, according to the chi-square analysis. Additionally, the classification of superstitious beliefs into three categories revealed that different percentages of the study population held low superstitious beliefs 21%, medium superstitions 54.1% and high superstitions 24.8% beliefs. The chi-square analysis revealed that the elderly, female, and low-educated patient groups were the highest in superstitious thinking. Multiple regression analysis revealed that educational level and superstitious thinking explained 0.223 of the treatment adherence variances. Treatment adherence is positively influenced by educational level ß (0.244) value, but superstitious thinking is negatively influenced by ß (-0.302) value. Conclusion: In conclusion, about half of the participants highly adhered. The results of the multiple-regression analysis indicate that superstition and education were two variables that impacted treatment adherence in this study. While superstitious beliefs lead to lower treatment adherence, education has the opposite effect. Finally, it is recommended to promote patient education to reduce superstitious beliefs, improve medication adherence.

Treatment non-adherence pattern among persons with neuropsychiatric disorders: A study from a rural community mental health centre in India.

BACKGROUND: Treatment gap causes significant loss to individuals, families, societies and the nation. Treatment adherence enhancement is a major challenge in psychiatric disorders. Globally, the community mental health services are obligated to minimize the treatment and adherence gap. In recent years' retrospective studies are gaining importance to measure the trend of mental health service utilization, cost effectiveness, resources allocation and similar aspects. AIM: To explore the treatment adherence pattern of persons with neuropsychiatric illness from a rural community mental health centre. METHOD: Five hundred and ninety-six medical records of persons with neuropsychiatric disorders who registered for outpatient treatment between 2015 and 2017 at Sakalawara Rural mental health centre of National Institute of Mental Health and Neuro Sciences, Bangalore, India, were reviewed to understand their adherence pattern. RESULTS: Out of 596 patients, 68 (11.4%) were referred to tertiary care mental health and District Mental Health Programme (DMHP) services. Out of the remaining 528 patients, 29.7% were regular to mental health services over a period of 12 months and above; majority of the patients (36.2%) dropped out of their treatment after their first contact and 34.1% discontinued their follow up visits over a period of first week to 12 months. CONCLUSION: Community based mental health centres too face challenges of and problems related to treatment non-adherence. Persons with neuropsychiatric disorders require continuity of care through regular home visits, out-reach services and innovative methods which will enhance treatment adherence.

Challenges in tracing treatment non-adherent persons with mental illness: Experiences from a rural community mental health center, India.

Identification, enrollment, and retention in treatment are challenging processes in mental health care. The present paper highlights the challenges in tracing and reenrolling non-adherent persons with mental illness for treatment in a rural community mental health center. Unclear address, phone numbers not in use, relocation from the given address, no further contact details etc. are the barriers to trace and make the home visits. A detailed review of the medical record, having a network with the village informal health care workers and groups, utilizing peer group support, etc., are the facilitators for tracing the treatment non-adherent persons in the community.

Medical neglect at a tertiary paediatric hospital.

Medical neglect is under-researched and the extent of the problem in Australia is unknown. We conducted a review of the referrals for medical neglect to the Child Protection Unit (CPU) at a tertiary children's hospital in Sydney over a 5 years period, from 2011 to 2016, to determine what medical conditions are being referred, the reason for the medical neglect concern and whether cases are managed in line with American Academy of Pediatrics (AAP) guideline on medical neglect. 61 cases of medical neglect were identified, constituting 4.1% of all referrals to the Child Protection Unit for physical abuse and neglect. There was a wide variety of medical conditions. Most were chronic medical conditions (87%). The top two medical conditions were chronic and complex multi-system disorders (37.7%) and endocrine disorders (18%). The majority of medical neglect were related to concerns that the caregivers were unwilling to follow medical advice (45.9%) or unable to provide necessary medical care (26.2%). In line with the AAP guideline on medical neglect, all cases were managed by addressing communication difficulties (100%) and resource issues were addressed in 80% of cases. A report to statutory child protection agencies was made in 50% of cases. Directly observed therapy and medical contracts were used in 30% and 26% of cases. We conclude that children with chronic medical conditions may be at risk of medical neglect. Communication difficulties were a factor in all cases. Statutory agency intervention is often required.

The Effect of Psychosocial Factors and Patients' Perception of Tuberculosis Treatment Non-Adherence in Addis Ababa, Ethiopia.

BACKGROUND: Although there are several studies reported on factors affecting tuberculosis (TB) treatment non-adherence, there is information gap on psychosocial and patients' perceptions aspects. Therefore, this study was aimed to investigate the effect of psychosocial factors and patients' perceptions on TB treatment non-adherence in Ethiopia. METHODS: A cross sectional study was conducted in Addis Ababa from May to December, 2014. Thirty one health facilities were randomly selected and 698 TB patients, who had been on treatment, were enrolled consecutively using patient registration number. Structured questionnaire was used to collect data on demographics, knowledge, psychological distress, alcohol use, tobacco smoking and six HBM domains. Treatment adherence level was the main outcome variable, and it measured using visual analog scale. Statistical Package for Social Sciences version 20 was used for data analysis. RESULTS: Non-adherence level within last one month prior to the study was 19.5%. After controlling for all potential confounding variables, Antiretroviral Therapy (ART) status (Adjusted Odds Ratio (AOR) = 1.79, 95% Confidence interval (CI) (1.09 -2.95)), alcohol use (AOR = 2.11, 95% CI (1.33-3.37)), economic status (AOR = 0.53, 95% CI (0.33-0.82)), perceived barriers (AOR = 1.21, 95% CI (1.10-1.47)) and psychological distress (AOR = 1.83, 95% CI (1.47-2.29)) were independently associated with TB treatment non-adherence. CONCLUSION: ART status, economic status, alcohol use, perceived barrier and psychological distress are the major areas that need to be targeted with health promotion intervention to enhance TB treatment adherence.

Reasons associated with treatment non-adherence in schizophrenia in a Pakistan cohort.

TREATMENT: non-adherence in patients with schizophrenia is the most common reason for a relapse of psychosis. In a cohort of participants in Pakistan who suffered a relapse of psychosis, we aimed to identify the principal factors associated with non-adherence, including any culture specific factors that might not be as significant in other jurisdictions. Semi-structured interviews were undertaken at four psychiatric hospitals in the Peshawar region in Pakistan with 55 participants (44 male and 11 female) diagnosed with schizophrenia, who had suffered a relapse of psychosis subsequent to treatment non-adherence. The five principal documented reasons for treatment non-adherence were: 1) alternative treatment pathway chosen with a traditional faith healers (n=53, 96.4%), 2) lack of insight (n=36, 65.5%), 3) poor economic status (n=33, 60.0%), 4) adverse effects of medications (n=33, 60.0%) and 5) utilising psycho-active substances as an alternative to psychotropic medications (n=27, 41.1%). A number of identified factors associated with a relapse of psychosis are potentially modifiable including the provision of a range of pharmacological options including second generation antipsychotic agents, long acting injectable antipsychotics and psycho-therapeutic interventions including psycho-education. These interventions should prove cost effective and be associated with reduced relapse rates of psychosis.

The use of randomisation-based efficacy estimators in non-inferiority trials.

BACKGROUND: In a non-inferiority (NI) trial, analysis based on the intention-to-treat (ITT) principle is anti-conservative, so current guidelines recommend analysing on a per-protocol (PP) population in addition. However, PP analysis relies on the often implausible assumption of no confounders. Randomisation-based efficacy estimators (RBEEs) allow for treatment non-adherence while maintaining a comparison of randomised groups. Fischer et al. have developed an approach for estimating RBEEs in randomised trials with two active treatments, a common feature of NI trials. The aim of this paper was to demonstrate the use of RBEEs in NI trials using this approach, and to appraise the feasibility of these estimators as the primary analysis in NI trials. METHODS: Two NI trials were used. One comparing two different dosing regimens for the maintenance of remission in people with ulcerative colitis (CODA), and the other comparing an orally administered treatment to an intravenously administered treatment in preventing skeletal-related events in patients with bone metastases from breast cancer (ZICE). Variables that predicted adherence in each of the trial arms, and were also independent of outcome, were sought in each of the studies. Structural mean models (SMMs) were fitted that conditioned on these variables, and the point estimates and confidence intervals compared to that found in the corresponding ITT and PP analyses. RESULTS: In the CODA study, no variables were found that differentially predicted treatment adherence while remaining independent of outcome. The SMM, using standard methodology, moved the point estimate closer to 0 (no difference between arms) compared to the ITT and PP analyses, but the confidence interval was still within the NI margin, indicating that the conclusions drawn would remain the same. In the ZICE study, cognitive functioning as measured by the corresponding domain of the QLQ-C30, and use of chemotherapy at baseline were both differentially associated with adherence while remaining independent of outcome. However, while the SMM again moved the point estimate closer to 0, the confidence interval was wide, overlapping with any NI margin that could be justified. CONCLUSION: Deriving RBEEs in NI trials with two active treatments can provide a randomisation-respecting estimate of treatment efficacy that accounts for treatment adherence, is straightforward to implement, but requires thorough planning during the design stage of the study to ensure that strong baseline predictors of treatment are captured. Extension of the approach to handle nonlinear outcome variables is also required. TRIAL REGISTRATION: The CODA study: ClinicalTrials.gov, identifier: NCT00708656 . Registered on 8 April 2008. The ZICE study trial: ClinicalTrials.gov, identifier: NCT00326820 . Registered on 16 May 2006.

The Relationship Between Eating Disorder Symptoms and Treatment Rejection among Young Adult Men in Residential Substance Use Treatment.

Research has demonstrated that individuals with substance use disorders (SUDs) and comorbid mental health problems evidence heightened negative consequences, including poorer treatment outcomes, a higher risk for relapse, and mortality compared to individuals with a single disorder. In this study, we focus on the comorbidity between SUDs and eating disorder (ED) symptomatology, as EDs are similarly associated with high rates of relapse, morbidity, and mortality. Of particular importance is research examining treatment rejection among individuals in treatment for SUDs with cooccurring ED symptomatology. This study seeks to add to the literature by examining treatment rejection among young adult men in residential treatment for SUDs (N = 68) with cooccurring ED symptomatology. Results from hierarchical regression analyses indicated that ED symptoms were significantly associated with treatment rejection after controlling for alcohol and drug use and problems and depression symptoms. Although this is a preliminary study, the results add to a growing body of research examining the comorbidity between SUDs and ED symptomatology. Future research examining this relationship is needed to further elucidate the treatment patterns among individuals with comorbid ED symptoms and substance use diagnoses.

Medical nonadherence in pediatric HIV: psychosocial risks and intersection with the child protection system for medical neglect.

Nonadherence to antiretroviral treatment has serious health implications for HIV-infected children, at times warranting referral to child protective services (CPS). The current study of 134 children with perinatally acquired HIV infection aimed to investigate rates of treatment adherence and CPS involvement, multilevel variables associated with nonadherence, and the manner in which these risks operated together in the prediction of adherence outcomes. Risk factors for nonadherence were grouped on the basis of confirmatory factor models, and factor score regression was carried out to determine which factors were uniquely predictive of adherence. A series of indirect effects models were then tested in order to examine how these factors operated together in the prediction of adherence. Results showed that almost half of the sample demonstrated suboptimal adherence to treatment, and in one-fifth, CPS was involved for medical neglect. Caregiver Health, Caregiver Involvement, Caregiver Acceptance, and Child Adaptation were predictive of nonadherence, and together explained 54% of the variance in treatment adherence. There were significant indirect effects of Caregiver Health on adherence that operated through Caregiver Involvement and Child Adaptation and an indirect effect of Caregiver Involvement on adherence through Child Adaptation. Findings extend current literature that has independently linked various factors predictive of medical adherence in pediatric HIV by showing separate but simultaneous associations with nonadherence and unique pathways to adherence involving multilevel risks. Healthcare and child welfare implications are discussed.