Mild depressive syndromes are highly prevalent among primary-care patients. Evidence-based treatment recommendations need to be derived directly from this diagnostically heterogeneous group. The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary-care patients, the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than randomization to a particular treatment. We conducted a randomized, placebo-controlled, single-centre, 10-wk trial with five arms: sertraline (flexible dosages up to 200 mg/d) (n = 83); placebo (n = 83); manual-guided cognitive-behavioural group therapy (one individual session and nine group sessions per 90 min) (n = 61); guided self-help group (control condition, n = 59); and treatment with sertraline or cognitive-behavioural group therapy according to patients' choice (n = 82). From 1099 consecutively screened adult patients, 368 formed the intent-to-treat population with milder forms of depression. Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores. Sertraline was superior to placebo (p = 0.03). Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy (p = 0.002) and compared to all other treatment arms including pill placebo (secondary analyses). Outcome in the patients' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy. Overall, sertraline is efficacious in primary-care patients with milder forms of depression. The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by 'nocebo' effects of the latter.
Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the ...
Ophthalmodynamometry can be relevant for momentary assessment and is not suitable for continuous monitoring. However, this technique can easily be repeated and may be used whenever increased ICP is suspected in a patient suffering from hydrocephalus, brain tumors, or head injury.
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