Real-World Treatment Patterns, Outcomes, Resource Utilization and Costs in Treatment-Resistant Major Depressive Disorder: PATTERN, a Retrospective Cohort Study in Belgium.

OBJECTIVE: Treatment-resistant depression (TRD), a subgroup of major depressive disorder (MDD) that does not adequately respond to treatment, has a substantial impact on the quality of life of patients and is associated with higher medical and mental health care costs. This study aimed to report real-world treatment patterns, outcomes, resource utilization, and costs in the management of TRD by psychiatrists in Belgium. METHODS: We conducted a retrospective, non-interventional cohort study of patients ≥ 18 years, with diagnosed MDD who are treatment-resistant, defined as not responding to two different antidepressant treatments in the current moderate to severe major depressive episode (MDE). Data obtained from medical records of patients included patient health state (MDE, response, remission, and recovery) and resource use (number of consultations and emergency room visits, non-drug and drug interventions, and hospitalizations). RESULTS: One hundred and twenty-five patients were enrolled in nine sites, with an average observation period of 34 months. During the MDE, 89.7% of patients were treated with selective serotonin reuptake inhibitors, 63.2% with serotonin-norepinephrine reuptake inhibitors, and 60.8% with anti-psychotics. Twenty-four percent of patients did not respond to any treatment; 76% responded, of whom 61% experienced a relapse; 28% of patients reached recovery, of whom 31.4% experienced recurrence. The average yearly direct cost of a TRD patient is €9012, mainly driven by hospitalization in the MDE. The observed absenteeism relates to a high indirect cost, representing 70% of the total MDE cost. CONCLUSION: TRD is associated with a high unmet need and economic burden for patients and society, with highest costs in the MDE health state driven by absenteeism.

Strangulation: a late presentation of right-sided diaphragmatic rupture.

A case of late presentation of a right-sided diaphragmatic rupture due to blunt chest trauma is presented. The patient suffered from strangulation of a herniated segment of small bowel into the chest. Chest radiography suggested diaphragmatic rupture, computed tomography and sonography established the correct preoperative diagnosis. The prevalence, mechanism of injury and possible complications are reviewed. The value of chest radiography and other imaging techniques is discussed.

Adult linear IgA bullous dermatosis with bronchial involvement.

A 54-year-old man is described, suffering from adult linear IgA bullous dermatosis with involvement of the bronchial mucosa. The main respiratory symptoms were recurring haemoptysis, episodic narrowing of the airways and persistent non-specific bronchial hyperreactivity. On CT scan the trachea had a saber-sheath shape with tracheal ring calcification. Endoscopically the tracheo-bronchial mucosa was diffusely purpuric and hyperaemic and also showed pale elevated plaques, bullous lesions and ulceration. Histological examination of biopsies of skin and nasal and tracheo-bronchial mucosa showed subepithelial blister formation associated with an accumulation of polymorphonuclear cells at the epithelial-subepithelial junction, and linear IgA deposits on direct immunofluorescence.

Once-daily dosing of a new ultrasustained-release theophylline preparation.

Theophylline plasma levels and profiles were evaluated in patients with chronic obstructive pulmonary disease during once-daily dosing of an ultrasustained-release theophylline preparation (Theo-1; capsules filled with microgranules containing 400 mg anhydrous theophylline). In a first study, 6 patients received a single morning dose of 800 mg (a) in the fasting state, and (b) with a protein-fat-rich breakfast in a random order, and the systemic theophylline availability was evaluated for 48 h. No significant differences were found either in Cmax (a: 7.0 +/- 3.2 micrograms/ml; b: 7.6 +/- 2.6 micrograms/ml), or in Tmax (a: 11.7 +/- 6.1 h; b: 10.2 +/- 3.6 h). Elimination half-life was in a 11.4 +/- 4.4 h and in b 12.9 +/- 4.8 h (p less than 0.05). In a second study, the steady-state theophylline levels were measured during a 24-hour dosage interval on day 8 after intake of 800 mg at 8 a.m. in 16 patients and at 8 p.m. in 11 patients. Plateau-shaped plasma concentration-time curves were obtained, with small fluctuations between the peak (Cmax) and trough (Cmin) levels: [100(Cmax-Cmin)/Cmin] was 83 +/- 40% after morning dose, and 54 +/- 26% after evening dose (p less than 0.05). Cmax was 12 +/- 5 and 11 +/- 4 micrograms/ml, respectively (NS). Tmax was 9 +/- 3 and 11 +/- 3 h, respectively (NS). The FDA fluctuation for the 37 patients was 48 +/- 20%. In a third study, the dose-plasma concentration relationship was evaluated in steady state in 6 patients receiving 400, 800 and 1,200 mg for 3 days each. The trough plasma concentrations were 2.6 +/- 0.9, 6.2 +/- 2.1 and 10.2 +/- 3.1 micrograms/ml, respectively. Six hours after drug intake the plasma levels were 5.0 +/- 1.6, 10.6 +/- 2.5 and 15.4 +/- 4.2 micrograms/ml, respectively; and 12 h after drug intake, 4.9 +/- 1.4, 11.6 +/- 2.4 and 14.5 +/- 3.7 micrograms/ml, respectively. In conclusion, we found in these studies that with once-daily dosing of the ultrasustained-release preparation Theo-1, plateau-shaped 24-hour theophylline plasma levels could be achieved. The relationship between daily dosage and theophylline plasma levels was linear intraindividually but showed an important interindividual variation. No consistent interference by food intake was found and no serious side effects occurred within therapeutic plasma levels.