Anna Szczepańska-Szerej

Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: results of an open-label, phase 3b study

Abstract Objective: This open-label, phase 3b study evaluated the effectiveness and tolerability of tapentadol prolonged release and tapentadol immediate release (for acute pain episodes) for severe, chronic low back pain with or without a neuropathic pain component that was inadequately managed in patients taking World Health Organization (WHO) Step I or II analgesics or who were not regularly treated with analgesics. Research design and methods: Average baseline pain intensity was greater than 5 (11-point numerical rating scale-3 [NRS-3; 3-day average pain intensity]) with WHO Step I or II analgesics and greater than 6 with no regular analgesic regimen. WHO Step II analgesics were discontinued before starting study treatment; WHO Step I analgesics or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50–250 mg bid) during a 5-week titration and 7-week maintenance period. Tapentadol immediate release was permitted for acute pain episodes (tapentadol prolonged release and immediate release maximum combined dose, ≤500 mg/day). The painDETECT questionnaire was used to define subsets of patients based on the probability of a neuropathic pain component to their low back pain as ‘negative’, ‘unclear’, or ‘positive’. Clinical trial registration: NCT00983385. Main outcome measure: The primary endpoint was the change from baseline to week 6 in average pain intensity (NRS-3), using the last observation carried forward to impute missing scores. Results: In the painDETECT negative (n = 49) and unclear/positive (n = 126) subsets, respectively, mean (SD) changes in pain intensity from baseline to week 6 were −2.4 (2.18) and −3.0 (2.07; both p < 0.0001). Among patients who had not received prior WHO Step II treatment, lower doses of tapentadol prolonged release were generally required with increasing likelihood of a neuropathic pain component. Based on the painDETECT questionnaire and the Neuropathic Pain Symptom Inventory (NPSI), tapentadol prolonged release treatment was also associated with significant improvements in neuropathic pain symptoms, with decreases in the number of pain attacks and the duration of spontaneous pain in the last 24 hours in patients with low back pain with a neuropathic pain component (painDETECT unclear or positive score at baseline or screening). The most common treatment-emergent adverse events (incidence ≥10%, n = 176) were nausea, dizziness, headache, dry mouth, fatigue, constipation, diarrhea, nasopharyngitis, and somnolence. Conclusions: Tapentadol prolonged release was well tolerated and effective for managing severe, chronic low back pain with or without a neuropathic pain component.

Predictors of depressive symptoms in patients with stroke – a three-month follow-up

BACKGROUND AND PURPOSE Depression is one of the most common post-stroke complications, which could impair rehabilitation outcome and quality of life, and could also increase mortality after stroke. The aim of the present study was to assess the association between demographic, socioeconomic and clinical (stroke risk factors, type of stroke, location of vascular lesion, cognitive functions) factors on the presence and severity of post-stroke depressive symptoms in patients after first ever stroke as well as on their social functioning. MATERIAL AND METHODS A prospective, cohort study with a three-month observation period was performed in seven centres. Severity of depressive symptoms was assessed with the help of a short, 15-item version of the Geriatric Depression Scale (GDS), 3 months after stroke onset. RESULTS On the basis of GDS (GDS Ł 5 points or > 5 points) patients were allocated to a group without (n = 160) or with symptoms suggestive of depression (n = 82). The study groups did not differ with respect to age, sex or place of residence. Univariate logistic regression analysis showed that independent predictors for the presence of symptoms suggestive of depression at 3 months after stroke were: low level of education, low income, greater severity of stroke, worse functional status, self-reported problems with daily-living activities and need of help in daily living activities. More than 60% of patients with depressive symptoms limited their social contacts. Patients with depressive symptoms were unsatisfied with their relations with life partners and friends. CONCLUSIONS Our study showed a complex aetiology of post-stroke depressive symptoms with an important role of socioeconomic factors. Depressive symptoms after stroke worsen existing health, social and economic problems, and cause social isolation of patients.

B-type natriuretic peptide as a marker of subclinical heart injury during mitoxantrone therapy in MS patients—Preliminary study

The aim of this study was to evaluate the plasma level changes of B-type natriuretic peptide (BNP), biochemical marker of heart failure, and echocardiographic parameters during mitoxantrone treatment in 22 multiple sclerosis (MS) patients (8 males, 14 females, mean age 37.1+/-6.6). Mitoxantrone (after mean cumulative dose of 58.0+/-7.0 mg/m(2)) did not alter left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), posterior wall thickness (PWT) and left ventricular end-diastolic volume (LVEDV). However, mean plasma level of BNP raised from 14.53+/-3.29 pg/ml at the baseline to 16.79+/-3.05 pg/ml and 18.83+/-4.90 pg/ml (P<0.01) after mean mitoxantrone dose of 30.7+/-5.9 mg/m(2) and 58.0+/-7.0 mg/m(2), respectively. These results strongly suggest subclinical myocardial dysfunction in mitoxantrone-treated group. We assume, that low-cost, repeated BNP measurements may be a good alternative for detection of early subtle myocardial injury in MS patients during routine mitoxantrone therapy.

The influence of hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (pravastatin) on gelatinase activity in vitro

Besides having lipid-lowering properties, statins (HMG-CoA reductase inhibitors) are known as strong anti-inflammatory agents reducing the expression of inducible matrix metalloproteinases (MMP). Our objective was to evaluate pravastatin effect (a hydrophilic statin) on serum gelatinase activities (MMP-2 and MMP-9) in vitro. Blood samples were obtained from 17 healthy individuals never treated with statins, and gelatinase activities were measured by gelatin zymography. After electrophoresis zymographic gels were incubated with or without pravastatin (5 μg/mL) for 18 h. We noticed that pravastatin enhances gelatinolytic activity at 72 kDa molecular mass (MMP-2) as well as at 130 kDa (MMP-9 heterodimer with neutrophil gelatinase-B associated lipocalin, NGAL) without significant effects on 92 kDa (MMP-9). The comparison of the above finding with previous studies suggests that statins can exert the opposite effects; the inhibition of MMP expression and the augmentation of its activity.

Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease

ABSTRACT We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14–3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

Correlation between CH2DS2-VASc Score and Serum Leptin Levels in Cardioembolic Stroke Patients: The Impact of Metabolic Syndrome

Objective To determine adipokines levels in patients with different etiologic subtypes of acute ischemic stroke (AIS) and metabolic syndrome (MetS) status. Methods Serum adiponectin, leptin, and resistin levels were determined by ELISA in 99 AIS patients and 59 stroke-free control group subjects. Stroke patients were grouped based on MetS, modified TOAST classification, and CHA2DS2-VASc scale in case of cardioembolic stroke following atrial fibrillation. Results No differences were found in all adipokine serum levels between AIS patients and appropriately matched control group. MetS-AIS patients had significantly higher leptin levels (22.71 ± 19.01 ng/ml versus 8.95 ± 9.22 ng/ml, p < 0.001) and lower adiponectin levels (10.71 ± 8.59 ng/ml versus 14.93 ± 10.95 ng/ml, p < 0.05) than non-MetS-AIS patients. In patients with cardioembolic stroke, leptin levels were significantly higher than in remaining stroke cases (19.57 ± 20.53 ng/ml versus 13.17 ± 12.36 ng/ml, p < 0.05) and CHA2DS2-VASc score positively correlated with leptin levels only (p < 0.001). Analysis of individual components of CHA2DS2-VASc score showed that hypertension, female gender, and diabetes had greatest impact on elevated serum leptin level. Conclusion This pilot study revealed that leptin could be a potential biomarker for risk stratification of cardioembolic stroke in MetS patients and that heterogeneity of stroke subtypes should be considered for more refined and precise clinical stroke studies.

The international normalized ratio (INR) as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

Abstract It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF). While oral anticoagulation with vitamin K antagonists (AVKs) substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR) in order to achieve therapeutic levels (2,0-3,0). The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2) were seen in thirty-five of these individuals (38,8%), while 55 (61,2%) showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.