Psychotherapy is an effective treatment for many common mental health problems, but the mechanisms of action and processes of change are unclear, perhaps driven by the focus on a single diagnosis... Show morePsychotherapy is an effective treatment for many common mental health problems, but the mechanisms of action and processes of change are unclear, perhaps driven by the focus on a single diagnosis which does not reflect the heterogeneous symptom experiences of many patients. The objective of this study was to better understand therapeutic change, by illustrating how symptoms evolve and interact during psychotherapy. Data from 113,608 patients from psychological therapy services who completed depression and anxiety symptom measures across three to six therapy sessions were analysed. A panel graphical vector-autoregression model was estimated in a model development sample (N = 68,165) and generalizability was tested in a confirmatory model, fitted to a separate (hold-out) sample of patients (N = 45,443). The model displayed an excellent fit and replicated in the confirmatory holdout sample. First, we found that nearly all symptoms were statistically related to each other (i.e. dense connectivity), indicating that no one symptom or association drives change. Second, the structure of symptom interrelations which emerged did not change across sessions. These findings provide a dynamic view of the process of symptom change during psychotherapy and give rise to several causal hypotheses relating to structure, mechanism, and process. Show less
Kay, J.; Harigai, M.; Rancourt, J.; Dickson, C.; Melby, T.; Issa, M.; ... ; Kremer, J.M. 2020
Objective To characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.Methods Data were pooled from eight randomised clinical trials (four phase 3,... Show moreObjective To characterise changes in selected haematological parameters following once-daily oral baricitinib dosing.Methods Data were pooled from eight randomised clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension. Changes in haematological parameters were evaluated up to 128 weeks (N=2387); overall safety of baricitinib was assessed up to 6 years (N=3492).Results Mean absolute neutrophil counts decreased (-1.36x10(9)/L) within 1 month, followed by stabilisation within the normal reference range through week 128. The incidence of serious infections was not elevated in patients with neutropenia during the 24-week placebo-controlled period. Mean lymphocyte counts increased (+0.30x10(9)/L) within 1 month, then decreased to baseline (weeks 12-24). Mean platelet counts increased at week 2 (+51x10(9)/L), then decreased towards baseline. Overall, mean haemoglobin concentrations decreased (-0.12 mmol/L), then returned to baseline; however, reduced baseline haemoglobin concentrations observed in the highest baseline high-sensitivity C reactive protein quartile increased over time. Permanent drug discontinuation occurred due to laboratory abnormalities related to neutrophil count in 8 (0.2%), lymphocyte counts in 6 (0.2%), platelet counts in 8 (0.2%), and haemoglobin levels in 16 (0.5%) of all baricitinib-treated patients (N=3492 with 7993 total person-years of exposure).Conclusions Moderate decreases in neutrophils were seen during baricitinib treatment; however, serious infection was uncommon in patients with neutropenia. Transient increases were observed in lymphocytes and platelets, which returned to baseline over time. Changes in haemoglobin concentration were generally small. Haematological abnormalities seldom led to drug discontinuation. Show less
