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Effectiveness of Varenicline as an Aid to Smoking Cessation in Primary Care: An Observational Study
(2012)
Aims: Although varenicline is commonly prescribed in primary care, information on smoking-related comorbidities and the effectiveness of varenicline in this context in Germany is scarce. This study assessed the efficacy and safety of varenicline in a large sample of patients seeking smoking cessation treatment through their general practitioners. The frequency of comorbidities was also evaluated. Methods: This was a 12-week, prospective, observational, non-comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were evaluated by verbal reporting using the nicotine use inventory. Results: Overall, 1,391 subjects were enrolled; 1,177 received study medication and were evaluated for effectiveness and safety. At the end of the study, 71.1% (95% confidence interval 68.5–73.7) of subjects were abstinent. There were a total of 205 all-causality adverse events; 2.2% were classified as serious or severe. There were no fatal adverse events. At inclusion, 66.7% of participants had at least 1 concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%), hypertension (29.6%) and depression (10.4%) being the most commonly reported. Conclusion: These real-world data indicate that varenicline is an effective and well-tolerated smoking cessation treatment when used in the primary care setting including patients with smoking-related comorbidities.
Abstract
In the 21st century, most of the world’s glaciers are expected to retreat due to further global warming. The range of this predicted retreat varies widely as a result of uncertainties in climate and glacier models. To calibrate and validate glacier models, past records of glacier mass balance are necessary, which often only span several decades. Long-term reconstructions of glacier mass balance could increase the precision of glacier models by providing the required calibration data. Here we show the possibility of applying shrub growth increments as an on-site proxy for glacier summer mass balance, exemplified by Salix shrubs in Finse, Norway. We further discuss the challenges which this method needs to meet and address the high potential of shrub growth increments for reconstructing glacier summer mass balance in remote areas.
Heart Rate Reduction by Ivabradine Improves Aortic Compliance in Apolipoprotein E-Deficient Mice
(2012)
Background: Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE<sup>–</sup>/<sup>–</sup>) mice. Methods: ApoE<sup>–</sup>/<sup>–</sup> mice fed a high-cholesterol diet and wild-type (WT) mice were treated with ivabradine (20 mg/kg/d) or vehicle for 6 weeks. Compliance of the ascending aorta was evaluated by MRI. Results: Ivabradine reduced heart rate by 113 ± 31 bpm (∼19%) in WT mice and by 133 ± 6 bpm (∼23%) in ApoE<sup>–</sup>/<sup>–</sup> mice. Compared to WT controls, ApoE<sup>–</sup>/<sup>–</sup> mice exhibited reduced distensibility and circumferential strain. HRR by ivabradine increased distensibility and circumferential strain in ApoE<sup>–</sup>/<sup>–</sup> mice but did not affect both parameters in WT mice. Ivabradine reduced aortic protein and mRNA expression of the angiotensin II type 1 (AT1) receptor and reduced rac1-GTPase activity in ApoE<sup>–</sup>/<sup>–</sup> mice. Moreover, membrane translocation of p47<sup>phox</sup> was inhibited. In ApoE<sup>–</sup>/<sup>–</sup> mice, HRR induced anti-inflammatory effects by reduction of aortic mRNA expression of IL-6, TNF-alpha and TGF-beta. Conclusion: HRR by ivabradine improves vascular compliance in ApoE<sup>–</sup>/<sup>–</sup> mice. Contributing mechanisms include downregulation of the AT1 receptor, attenuation of oxidative stress and modulation of inflammatory cytokine expression.
In order to identify possible experimental signatures of the superfluid to Mott-insulator quantum phase transition we calculate the charge structure factor S(k, ω) for the one-dimensional Bose-Hubbard model using the dynamical density-matrix renormalisation group (DDMRG) technique. Particularly we analyse the behaviour of S(k, ω) by varying – at zero temperature–the Coulomb interaction strength within the first Mott lobe. For strong interactions, in the Mott-insulator phase, we demonstrate that the DDMRG results are well reproduced by a strong-coupling expansion, just as the quasi-particle dispersion. In the super-fluid phase we determine the linear excitation spectrum near k = 0. In one dimension, the amplitude mode is absent which mean-field theory suggests for higher dimensions.
Background: Controversy surrounds the questions whether co-occurring depression has negative effects on cognitivebehavioral therapy (CBT) outcomes in patients with panic disorder (PD) and agoraphobia (AG) and whether treatment for PD and AG (PD/AG) also reduces depressive symptomatology. Methods: Post-hoc analyses of randomized clinical trial data of 369 outpatients with primary PD/AG (DSM-IV-TR criteria) treated with a 12-session manualized CBT (n = 301) and a waitlist control group (n = 68). Patients with comorbid depression (DSM-IV-TR major depression, dysthymia, or both: 43.2% CBT, 42.7% controls) were compared to patients without depression regarding anxiety and depression outcomes (Clinical Global Impression Scale [CGI], Hamilton Anxiety Rating Scale [HAM-A], number of panic attacks, Mobility Inventory [MI], Panic and Agoraphobia Scale, Beck Depression Inventory) at post-treatment and follow-up (categorical). Further, the role of severity of depressive symptoms on anxiety/depression outcome measures was examined (dimensional). Results: Comorbid depression did not have a significant overall effect on anxiety outcomes at post-treatment and follow-up, except for slightly diminished post-treatment effect sizes for clinician-rated CGI (p = 0.03) and HAM-A (p = 0.008) when adjusting for baseline anxiety severity. In the dimensional model, higher baseline depression scores were associated with lower effect sizes at post-treatment (except for MI), but not at follow-up (except for HAM-A). Depressive symptoms improved irrespective of the presence of depression. Conclusions: Exposure-based CBT for primary PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbid depression or depressive symptomatology.
Patients with atrial fibrillation (AF) often present with typical angina pectoris and mildly elevated levels of cardiac troponin (non-ST-segment elevation myocardial infarction) during an acute episode of AF. However, in a large proportion of these patients, significant coronary artery disease is excluded by coronary angiography, which suggests that AF itself influences myocardial blood flow. The present review summarizes the effect of AF on the occurrence of ventricular oxidative stress, redox-sensitive signaling pathways and gene expression, and microcirculatory flow abnormalities in the left ventricle.
Background: To analyze the relation and distribution of mean, systolic and diastolic ocular perfusion pressure (OPP) in telemedical homemonitoring of patients with primary open-angle glaucoma (POAG). Methods: 70 patients with POAG measured intraocular pressure (IOP) and blood pressure at home for a period of 6 months with the Goldmann applanation self-tonometer Ocuton S and the blood pressure device boso medicus PC. Twenty-four-hour profiles were taken every 4 weeks in addition to single measurements in the morning and evening once a week. All measured values were transmitted to an electronic patient record, which calculated OPP by taking systolic, diastolic and mean arterial blood pressure and subtracting IOP. Results: We analyzed 3,282 values of mean, systolic and diastolic OPP. The quantity of values below the risk levels of the Barbados Eye Studies was calculated. We found values lower than the risk levels for LE: 49 (1.5%)/RE: 60 (1.8%) systolic OPP, LE: 1,623 (49.5%)/RE: 1,761 (53.7%) diastolic OPP and LE: 687 (20.9%)/RE: 794 (24.2%) mean OPP. The individual average OPP levels of all 70 patients below the risk levels showed the following distribution: LE: 4 (5.7%)/RE: 6 (8.6%) systolic OPP, LE: 19 (27.1%)/RE: 20 (28.6%) diastolic OPP and LE: 10 (14.3%)/RE: 10 (14.3%) mean OPP. Conclusion: The individual distribution of different OPP values in POAG patients is not easy to interpret for clinical ophthalmologists. Precise practicable guidelines for clinical use still have to be determined.
Background: In clinical practice, treatment of genital tract infections is based on administration of either antibiotics or antiseptics. While antibiotics may be applied systemically or topically, antiseptics may be applied only topically. In case of bacterial vaginosis (BV), antibiotic therapy may often be limited and side effects due to systemic administration may develop. Polihexanide (PHMB) is a promising option for the topical treatment of genital tract infections, in particular BV and vaginitis. Method: A systematic search for publications on the use of PHMB for the treatment of genital infections in two electronic databases was performed. Titles, abstracts and citations were imported into a reference database. Duplicates were removed and two reviewers assessed each identified publication separately. Results: Among a total of 204 references, 3 prospective randomized trials were identified. Two trials treated BV infections with PHMB in comparison to clindamycin as antibiotic standard therapy with no significant differences either in safety or in efficacy. The third controlled trial investigated the clinical efficacy of PHMB compared to placebo in the treatment of human papilloma virus. Patients treated with PHMB daily for up to 16-weeks showed significantly higher (52%) clearance of genital warts as compared to patients treated with placebo (4%). Conclusion: PHMB may be a clinically effective alternative for the treatment of BV and human papilloma virus. Although PHMB-based antiseptics are available since the late 90s, controlled trials to investigate its clinical potential for antiseptic treatment are scant. Clinical use of antiseptics for the treatment of infectious diseases should be explored and supported further.
Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area.
Background: Among the five somatostatin receptors (sst<sub>1</sub>-sst<sub>5</sub>), the sst<sub>3</sub> receptor displays a distinct pharmacological profile. Like sst<sub>2</sub>, the sst<sub>3</sub> receptor efficiently internalizes radiolabeled somatostatin analogs. Unlike sst<sub>2</sub>, however, internalized sst<sub>3</sub> receptors are rapidly transferred to lysosomes for degradation. Apart from this, very little is known about the clinical relevance of the sst<sub>3</sub> receptor, which may in part be due to the lack of specific monoclonal sst<sub>3</sub> antibodies. Methods: Here, we have extensively characterized the novel rabbit monoclonal anti-human sst<sub>3</sub> antibody UMB-5 using transfected cells and receptor-expressing tissues. UMB-5 was then subjected to immunohistochemical staining of a series of 190 formalin-fixed, paraffin-embedded normal and neoplastic human tissues. Results: Specificity of UMB-5 was demonstrated by detection of a broad band migrating at a molecular weight of 70,000–85,000 in immunoblots from human pituitary. After enzymatic deglycosylation, the size of this band decreased to a molecular weight of 45,000. Tissue immunostaining was completely abolished by pre-adsorption of UMB-5 with its immunizing peptide. In addition, UMB-5 detected distinct cell populations in human tissues like pancreatic islands, anterior pituitary, adrenal cortex, adrenal medulla, and enteric ganglia, similar to that seen with a rabbit polyclonal antibody generated against a different carboxyl-terminal epitope of the sst<sub>3</sub> receptor. In a comparative immunohistochemical study, UMB-5 yielded predominant plasma membrane staining in the majority of pituitary adenomas, pheochromocytomas, and a subset of neuroendocrine tumors. The sst<sub>3</sub> receptor was also present in many glioblastomas, pancreatic, breast, cervix, and ovarian carcinomas. Conclusion: The rabbit monoclonal antibody UMB-5 may prove of great value in the identification of sst<sub>3</sub>-expressing tumors during routine histopathological examinations. Given its unique trafficking properties, these tumors may be potential candidates for sst<sub>3</sub>-directed receptor radiotherapy.