What are patients' experiences of discontinuing clozapine and how does this impact their views on subsequent treatment?

BACKGROUND: Discontinuing what is considered the most effective treatment for treatment-resistant schizophrenia may precipitate feelings of failure or a relapse of illness. Clozapine treatment is discontinued for a variety of reasons, including non-adherence, intolerance, or lack of efficacy. Patients' experiences of discontinuing the "best" treatment and the impact on perceptions of subsequent antipsychotic treatment are important in developing an understanding of the factors affecting people's treatment choices. This study is the first of its type, seeking to explore people's perspectives on clozapine discontinuation. METHOD: Semi-structured interviews with sixteen patients who had received clozapine and discontinued treatment-thirteen males and three females, age range: thirty-two to seventy-eight years old-were audio-recorded and transcribed. A modified inductive approach to analysis, based on grounded theory, was taken to identify commonalities and differences in patients' perceptions. RESULTS: The three main themes identified from participants' experiences were: (1) positive and negative effects of treatment; (2) feelings of agency, being the capacity to make decisions about treatment and act independently; (3) choice of treatment in the future. Participants exhibited agency in making choices about medication, including risking relapse, while attempting self-management of medication effects. Different participants perceived the same side effect as beneficial or intolerable. Variation in subsequent treatment choices was reported, with some participants favouring depot (long-acting) injections. A participant was frightened when not told about clozapine's side effects, which led to the participant not being engaged in future treatment decisions. Others, despite suffering serious adverse effects, retained positive perceptions of clozapine; they experienced despair at finding an effective alternative. CONCLUSIONS: Experiences with clozapine discontinuation evoked powerful emotions and resulted in clozapine being the benchmark for other treatments. Knowledge, agency, and being in control were important to participants in relation to treatment. Personal perceptions of treatments or beliefs about illness could lead to non-adherence. People value the clinician listening to their experiences to better understand their perspective, enabling concerns about medication to be addressed through true shared decision making. TRIAL REGISTRATION: NHS Health Research Authority and Health and Care Research Wales, IRAS Project ID 225753, Research Ethics Committee (REC) reference: 18/NW/0413, 25/06/2018.

Reply: External validation of the OPALS prediction model for in-hospital mortality in patients with acute decompensated pulmonary hypertension.

The OPALS score appears to be a promising PH-specific tool for predicting outcomes in medically decompensated patients https://bit.ly/3rTxzbr.

Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry.

Pulmonary hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce. We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000-2017 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer term outcomes in survivors to hospital discharge. 242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons, respectively. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II (Acute Physiology and Chronic Health Evaluation) score, age and lactate, and lower oxygen saturation measure by pulse oximetry/inspiratory oxygen fraction (S pO2 /F iO2 ) ratio, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (oxygen (S pO2 /F iO2 ) ≤185; platelets ≤196×109·L-1; age ≥37.5 years; lactate ≥2.45 mmol·L-1; sodium ≤130.5 mmol·L-1), identified medical patients at increasing risk of hospital mortality. One (11%) out of nine patients who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge. These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation.

Effects of modest iron loading on iron indices in healthy individuals.

Intravenous iron administration is typically indicated in individuals who have iron deficiency refractory to oral iron. However, in certain chronic disease states such as heart failure, it may be beneficial to administer intravenous iron to individuals who are not strictly iron deficient. The purpose of this study was to define a dose-response relationship between clinical indices of iron status and modest loading with intravenous iron in healthy, iron-replete participants. This was a double-blind, controlled study involving 18 male participants. Participants were block-randomized 2:1 to the iron and saline (control) groups. Participants in the iron group received 3.75 mg/kg body wt up to a maximum of 250 mg of intravenous iron, once a month for 6 mo, provided that their ferritin remained measured <300 µg/l within the week before a dose was due and their transferrin saturation remained <45%. Otherwise they received a saline infusion, as did the control participants. Iron indices were measured monthly during the study. The pulmonary vascular response to sustained hypoxia and total hemoglobin mass were measured before, at 3 mo (hemoglobin mass only), and at 6 mo as variables that may be affected by iron loading. Serum ferritin was robustly elevated by intravenous iron by 0.21 µg·l-1·mg-1 of iron delivered (95% confidence interval: 0.15-0.26 µg·l-1·mg-1), but the effects on all other iron indices did not reach statistical significance. The pulmonary vascular response to sustained hypoxia was significantly suppressed by iron loading at 6 mo, but the hemoglobin mass was unaffected. We conclude that the robust effect on ferritin provides a quantitative measure for the degree of iron loading in iron-replete individuals.NEW & NOTEWORTHY There has been an increasing interest in administering intravenous iron to patients to alter their iron status. Here, we explore various indices of iron loading and show that in healthy volunteers serum ferritin provides a robust indicator of the amount of iron loaded, with a value of 21 µg/l increase in ferritin per 100 mg of iron loaded.