Evaluation of an online-based self-help program for patients with generalized anxiety disorder - A randomized controlled trial.

Objectives: This study aimed to evaluate the effects of an online self-help intervention for generalized anxiety disorder (GAD). Our primary outcomes were generalized anxiety symptoms, measured using the Generalized Anxiety Disorder - 7 (GAD-7; Spitzer et al., 2006), and wellbeing based on the World Health Organization Wellbeing Index - 5 (WHO-5; Topp et al., 2015). Methods: A total of 156 German-speaking patients aged 18 to 65 with a diagnosis of GAD and internet access were included in this randomized controlled trial. The intervention group (N = 78) received access to a 12-week online self-help program, while the waitlist control group (N = 78) received access after the 12-week waiting period. Results: The intervention group showed a significant improvement in generalized anxiety symptoms compared to the control group (t(df = 123.73) = 4.52, p < .001) with a large effect size (d = 0.88, 95 %-CI: 0.50; 1.26). Additionally, the intervention group demonstrated a significant increase in wellbeing compared to the control group (t(df = 87,86) = 3.48, p < .001), with a moderate effect size (d = 0.62, 95 % CI: 0.27; 0.98). However, no significant effects were observed for secondary outcomes of functional impairments, work productivity, mental health literacy, and healthcare demands. For exploratory outcomes, improvement was found for anxiety and worry symptoms. Conclusions: These findings suggest that an online-based self-help intervention effectively reduces GAD symptoms and improves overall wellbeing. Future research should explore the long-term effects of this intervention and investigate potential mechanisms underlying its efficacy. Public health implications: Online-based self-help programs provide a promising treatment option for individuals with GAD who face barriers to traditional face-to-face therapy.

Efavirenz plasma levels for the prediction of treatment failure in heavily pretreated HIV-1 infected patients.

OBJECTIVE: Efavirenz (EFV) plasma levels have been discussed as a predictor of treatment failure in HIV infected patients. The aim of this prospective, open-labeled, case-control study was to evaluate pretreated patients in regards to efavirenz plasma levels and efficacy of therapy. METHODS: Blood samples were obtained monthly from 33 patients receiving efavirenz in combination with other antiretroviral agents for at least 3 months. EFV plasma concentrations and potease inhibitor (PI) plasma levels were measured by high-performance liquid chromatography (HPLC). EFV plasma levels were correlated with efficacy. In patients with virologic failure genotypic resistance testing was performed. RESULTS: Mean efavirenz plasma levels (n = 240) of 33 patients were 3.119 +/- 2.497 ng/ml. There were no significant differences between median efavirenz plasma levels of 24 patients (72%) with a HIV-RNA < 20 copies/ml (2.168 ng/ml), 3 patients with HIV-RNA of 20 500 copies/ml (3.362 ng/ml), and 6 patients with a virologic failure (>500 copies/ml) (2.190 ng/ml) respectively. Efavirenz plasma levels below 1.000 ng/ml were found in 4/27 effective treated patients, and in 4/6 patients with virologic failure. In all patients with virologic failure multiple NRTI, NNRTI and PI mutations were found in genotypic resistance testing. CONCLUSION: An individual EFV plasma level below 1.000 ng/ml in one single measurement seems to be predictive of viral failure and the developement of genotypic resistance. Therapeutic drug monitoring of EFV might be helpful, especially in heavily pretreated patients, to reach long term sufficently effectiveness of therapy.

Triple antiviral re-therapy for chronic hepatitis C with interferon-alpha, ribavirin and amantadine in nonresponders to interferon-alpha and ribavirin.

BACKGROUND: Therapy options for patients with chronic hepatitis C who failed prior treatment are needed. In recent studies triple antiviral therapy with Interferon-alpha, ribavirin, and amantadine seemed to increase sustained virological response rates in this group. METHOD: To evaluate efficacy, side effects and safety of a triple re-therapy in an open labeled prospective study, we compared 23 nonresponders to interferon monotherapy (9 nonresponders, 3 relapsers, 11 with breakthrough) with 23 nonresponders to standard combination therapy (interferon plus ribavirin) (16 nonresponders, 7 breakthroughs). All outpatients enrolled for re-therapy received interferon-alpha 2a (6 mega units [MU] three times in week), ribavirin (1000-1200 mg daily in divided doses) and amantadine (200 mg daily) for six months. In case of virological re-therapy response (negative qualitative HCV RNA) study medication was continued with interferon monotherapy for another six months. RESULTS: Sustained virological response was achieved in 16 (35%) out of 46 prior therapy nonresponders. Response rates were dependent on pretreatment outcome. In the standard combination therapy group only 1 (6%) primary nonresponder achieved sustained response, but none of the 9 monotherapy nonresponders did. After primary breakthrough sustained response was seen in 8 of 11 (73%) patients in the interferon monotherapy and in 5 of 7 (71%) in the combination therapy group. Of 3 monotherapy relapsers 2 (66%) did also clear the virus sustained. Safety profile under triple therapy was similar to the previous therapy. Compliance was higher and side effects lower in those patients already experienced in combination therapy. CONCLUSION: In patients with a breakthrough or relapse after interferon monotherapy or standard combination therapy with interferon and ribavirin a re-therapy with a triple combination of interferon, ribavirin, and amantadine results in a high rate of sustained virological response.

Therapeutic drug monitoring of indinavir in HIV-infected patients undergoing HAART.

BACKGROUND: Therapeutic drug monitoring (TDM) of protease inhibitors (PI) is gaining increasing importance for the management of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). The PI indinavir (IDV) is widely used in HAART regimens. Combinations of IDV with ritonavir (RTV) have been used to increase the plasma concentration of IDV. However, the desirable IDV concentration range in clinical practice remains to be elucidated. PATIENTS AND METHODS: To study the value of TDM for IDV in clinical practice, a retrospective analysis of 501 plasma samples of patients treated with IDV in various dosages was performed. IDV levels were determined during routine outpatient visits. Analysis was performed by high pressure liquid chromatography (HPlC) with UV detection. RESULTS: A widespread range of IDV plasma concentrations was seen both within and between patients. The mean IDV level during therapy with IDV 2.4 g/d was 3,260 ng/ml (95% CI: 2,903 ng/ml; 3,618 ng/ml). IDV levels at a dose of IDV 1.6 g/d in combination with RTV resulted in a mean IDV plasma concentration of 4,191 ng/ml (95% CI: 3,356 ng/ml; 5,026 ng/ml). There was no significant difference between plasma levels at the doses of 2.4 g/d and 1.6 g/d. 35 of all 130 patients treated with IDV reached only suboptimal IDV plasma concentrations below the limit of 150 ng/ml. There was no statistically significant difference between the number of patients below an IDV plasma concentration of 150 ng/ml in the various dosage regimens. CONCLUSION: During therapy with IDV in a b.i.d. scheme, similar IDV plasma concentrations and a comparable number of patients with subinhibitory plasma concentrations were observed when compared to a therapeutic regimen with t.i.d. dosing. In this study, even at various times of plasma sampling after oral ingestion, TCM facilitated the surveillance of patients compliance.

High-performance liquid chromatographic method for the determination of HIV-1 non-nucleoside reverse transcriptase inhibitor efavirenz in plasma of patients during highly active antiretroviral therapy.

A new high-performance liquid chromatographic method for the determination of efavirenz in human plasma is described. Quantitative recovery following liquid-liquid extraction with diethylether from 200 microl of human plasma was achieved. Subsequently, the assay was performed with 67 mM potassium dihydrogen phosphate-acetonitrile as a mobile phase, a XTerraRP 18 column protected with a Phenomenex C18 column and UV detection at 246 nm. Linear standard curves were obtained for concentrations ranging from 25 to 15,000 ng/ml. The calculated intra- and inter-day coefficients of variation were below 10%.

Influence of smoking on cotinine and caffeine plasma levels in patients with alcoholic liver cirrhosis.

BACKGROUND: Retention of caffeine was observed in patients with alcoholic liver cirrhosis and impaired liver function. Cotinine, the major metabolite of nicotine, is transformed by microsomal N-oxidation to secondary metabolites. The aim of this study was to investigate if impaired liver function leads to a retention of cotinine in a similar way to caffeine retention. Furthermure the influence of smoking on cotinine and caffeine plasma levels was studied. METHODS: 91 smokers and 12 nonsmokers with alcoholic liver cirrhosis were subdivided according to their smoking habits. Cotinine plasma levels and fasting caffeine concentrations were measured by a gaschromatographic method. Concentrations of conjugated bile acids were measured by RIA. 10 healthy smokers and 11 nonsmokers were used as a control group. RESULTS: Mean plasma cotinine concentrations found in slight smokers (200 +/- 155 ng/ml), intermediate smokers (384 +/- 223 ng/ml) and heavy smokers (430 +/- 266 ng/ml) with alcoholic liver cirrhosis were significantly higher than in healthy, smoking volunteers with slight, intermediate, and heavy smoking (101 +/- 14; 274 +/- 112; 345 +/- 85 ng/ml) (p <0.01) respectively. In nonsmokers with alcoholic liver cirrhosis plasma cotinine (44 +/- 25 ng/ml) was significantly elevated compared to healthy nonsmokers (27 +/- 19 ng/ml) (p <0.01). - Fasting caffeine plasma levels in patients with alcoholic liver cirrhosis (4.00 +/- 5. 20 microg/ml) were significantly higher than in healthy volunteers (0.91 +/- 0.42 microg/ml) (p <0.01). A decrease of plasma levels was observed in correlation to the amount of smoking in patients with alcoholic cirrhosis (slight smokers: 7.67 +/- 8.54 microg/ml, intermediate smokers: 3.35 +/- 2.91 microg/ml and heavy smokers: 2. 48 +/- 2.68 microg/ml). Conjugated bile acids were elevated in patients with alcoholic liver cirrhosis to 32,56 +/- 38,24 mmol/l. CONCLUSIONS: Increased cotinine plasma levels in smokers and nonsmokers with alcoholic liver cirrhosis demonstrate a cotinine retention in patients with impaired liver function. The inducing effect of smoking is shown by a decrease of fasting caffeine plasma concentrations.

Therapeutic drug monitoring of saquinavir in patients during protease inhibitor therapy with saquinavir alone or in combination with ritonavir or nelfinavir.

Therapeutic drug monitoring is essential in HIV-patients undergoing highly active antiretroviral therapy (HAART). Saquinavir (SQV) is used alone or in combination with ritonavir (RTV) or nelfinavir (NLF), respectively, in the context of the HAART drug regimen. The achievable SQV concentration range in clinical practice remains to be elucidated. A non-randomized prospecitve clinical trial 19 patients (group I) receiving SQV (1x600 mg/d Invirase or Fortovase), 29 patients (group II) receiving SQV (2x600 mg/d Fortovase) plus RTV (2x400 mg/d Norvir), and 21 patients (group III) receiving SQV (2x600 mg/d Fortovase) plus NLF (2x750 mg/d Viracept) was conducted to determine SQV plasma concentrations. SQV levels were determined as trough levels during routine outpatient visits. Analysis was performed by HPLC with UV detection. The lowest SQV plasma levels were found in group I (95% CI 89-177 ng/ml). Significantly higher SQV levels were found in group III (combination with NLF) ranging from 242 to 398 ng/ml (95% CI) and in group II (combination with RTV) ranging from 1354 to 1747 ng/ml (95% CI). The IC 50% of 54 ng/ml was not reached in at least one sample during the study (mean duration of study 16+/-10 months) in 14/19 patients of group I, 9/29 patients in group II and 13/21 patients in group III, respectively. A positive correlation between patient compliance, defined by SQV levels in the 95% CI of the used combination, and the HIV RNA plasma level was found. The presented data confirm that therapy with SQV alone may not be effective, since trough levels are near the lower limit of antiretroviral efficacy. Although the combination of SQV with NLF results in higher SQV plasma concentrations in a bid regimen, in more than 60% of the patients SQV concentrations below IC 50 level were detected during the twelve-months study period. The combination of SQV with RTV yields the highest SQV-trough levels. SQV concentrations below the IC 50 were seen in only 31% of patients with the SQV/RTV combination. In conclusion, therapeutic drug monitoring allows an efficient surveillance of patients compliance. In addition, therapeutic drug monitoring represents a valuable tool for management of HAART in patients receiving a complex comedication or suffering from advanced liver disease.