Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

Will I or my loved one die? Concordant awareness between terminal cancer patients and their caregivers is associated with lower patient anxiety and caregiver burden.

OBJECTIVE: The aims of this study were to investigate the association between patients' awareness of their terminal illness and the levels of anxiety and depression, whether the concordance between the patients' and caregivers' belief about the patient's terminal illness was associated with patient's anxiety and depression, and with the caregiver burden. METHOD: The study recruited 31 terminally ill patients with cancer along with their caregivers from a Palliative Care Unit. All data about patients and caregivers' awareness of the illness, patients' depression and anxiety, and caregiver burden were collected. RESULTS: Patients aware of their short-term prognosis of death showed lower levels of anxiety than the unaware ones, especially women. Aware patients with concordant caregivers showed lower levels of anxiety but not of depression. Caregivers concordant with the patients' awareness presented lower levels of strain and burden. Finally, terminal patients who had an adult child caregiver were less likely to be aware of their terminal condition. CONCLUSIONS: It appears that illness awareness and the caregiver's concordance with the patient's belief on the terminal condition are associated with lower anxiety, especially in women, and a reduced burden for caregivers.