A PROSPECTIVE OBSERVATIONAL STUDY TO ASSESS WAITING TIMES TO FIRST TREATMENT IN PATIENTS DIAGNOSED WITH BRAIN TUMOR.

The aim was to investigate and determine waiting intervals from diagnosis to first treatment in brain tumor patients. A prospective observational study was performed at the Department of Neurology, Split University Hospital Center, Split, Croatia, from February 21, 2016 until April 10, 2017. The inclusion criterion was the diagnosis of brain tumor confirmed by standard neuroimaging methods. The diagnosis-to-treatment interval (DTI) was defined as the time interval between the date of confirmed radiological diagnosis and the initiation of definitive treatment. Out of 73 patients diagnosed with brain tumor, 3 of them died, 16 were discharged for symptomatic treatment, and the rest were cured by surgical and/or oncologic procedures. The median DTI for any kind of treatment was 15.5 days. The median DTI for radio-guided and resection surgery was 14 days, while the median DTI for the initial oncologic treatment was 42 days. The median DTI of 15.5 days for brain tumors is still, by a wide margin, beyond the preferable one-digit number. When compared to the available data from other countries, however, it seems that the health system in Croatia provides the same, if not a slightly higher, level of efficiency. The median DTI for primary oncologic treatment did, however, indicate a substantial delay.

Psychometric validation of the Croatian version of the Quality of Life in Epilepsy Inventory (QOLIE-31).

The primary goals of this study were to adapt the Quality of Life in Epilepsy Inventory-31 items (QOLIE-31) questionnaire to the Croatian language and to assess the translated questionnaire's psychometric properties. Translation/retranslation of the English version of the QOLIE-31 was done, and all steps for cross-cultural adaptation process were performed properly by an expert committee. Later, QOLIE-31 questionnaires and previously validated Short Form-36 (SF-36) outcome instruments were given to 200 patients with epilepsy. 172 patients (86%) responded to the first set of questionnaires, and 114 of the first time respondents (66%) returned their second survey. The two measures of reliability as internal consistency and reproducibility were determined by Cronbach alpha statistics and intraclass correlation coefficient, respectively. Concurrent validity was measured by comparing with a SF-36 questionnaire, and measurement was made using the Pearson correlation coefficient (r). The study demonstrated satisfactory internal consistency with high Cronbach a values for all of the corresponding domains (seizure worry 0.84, medication effects 0.80, emotional well-being 0.73, energy/fatigue 0.76, cognitive functioning 0.71, social functioning 0.77, overall quality of life 0.65). The intraclass correlation coefficient for six domains of QOLIE-31 questionnaire demonstrated excellent test/retest reproducibility (ICC > or = 0.75), and good test/retest reproducibility (ICC 0.71) in one domain (cognitive functioning). Considering concurrent validity, three domains had excellent correlation (r = 0.75-1), while 11 had good correlation (r = 0.50 to 0.75), and 3 had moderate correlation (r = 0.25-0.50). This study demonstrated that, if measures are to be used across cultures, the items must not only be translated well linguistically but also must be culturally adapted to maintain the content validity of the instrument at a conceptual level across different cultures. Croatian version of QOLIE-31 will be a valuable contribution to outcome measurement in epilepsy patients, particularly in the context of treatment trials, but als in a wider research context.

Peripheral chemoreflex regulation of sympathetic vasomotor tone in apnea divers.

OBJECTIVES: Involuntary apnea episodes in obstructive sleep apnea patients result in selective potentiation of peripheral chemoreceptor regulation of sympathetic vasomotor tone. Breath-hold diving is associated with repeated "voluntary" apnea episodes and massive arterial oxygen desaturation, which could also perturb chemoreflex function. METHODS: We measured ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 11 breath-hold divers and eleven matched control subjects. The study was carried out at least 1 month after intense apnea training. RESULTS: Baseline MSNA frequency was 30 +/- 4 bursts/min in control subjects and 31 +/- 7 bursts/min in divers (ns). During hypoxia MSNA frequency and total activity increased similarly in both groups (30 and 66% in controls and 27 and 60% in divers, respectively). MSNA remained increased after termination of hypoxia and approached baseline measurements after 20 min. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia-induced tachycardia drove an increase in cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. INTERPRETATION: We conclude that after the end of intensive training/competition periods, apnea divers show normal peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone. Although voluntary apnea may not lead to sustained changes in sympathetic nervous system regulation, we cannot exclude the possibility that repeated sympathetic activation elicited by voluntary apnea imposes a burden on the cardiovascular system.

Glossopharyngeal insufflation induces cardioinhibitory syncope in apnea divers.

Apnea divers increase intrathoracic pressure voluntarily by taking a deep breath followed by glossopharyngeal insufflation. Because apnea divers sometimes experience hypotension and syncope during the maneuver, they may serve as a model to study the mechanisms of syncope. We recorded changes in hemodynamics and sympathetic vasomotor tone with microneurography during breath holding with glossopharyngeal insufflation. Five men became hypotensive and fainted during breath holding with glossopharyngeal insufflation within the first minute. In four divers, heart rate dropped suddenly to a minimum of 38 ± 4 beats/min. Therefore, cardioinhibitory syncope was more common than low cardiac output syncope.

Central chemoreflex sensitivity and sympathetic neural outflow in elite breath-hold divers.

Repeated hypoxemia in obstructive sleep apnea patients increases sympathetic activity, thereby promoting arterial hypertension. Elite breath-holding divers are exposed to similar apneic episodes and hypoxemia. We hypothesized that trained divers would have increased resting sympathetic activity and blood pressure, as well as an excessive sympathetic nervous system response to hypercapnia. We recruited 11 experienced divers and 9 control subjects. During the diving season preceding the study, divers participated in 7.3 +/- 1.2 diving fish-catching competitions and 76.4 +/- 14.6 apnea training sessions with the last apnea 3-5 days before testing. We monitored beat-by-beat blood pressure, heart rate, femoral artery blood flow, respiration, end-tidal CO(2), and muscle sympathetic nerve activity (MSNA). After a baseline period, subjects began to rebreathe a hyperoxic gas mixture to raise end-tidal CO(2) to 60 Torr. Baseline MSNA frequency was 31 +/- 11 bursts/min in divers and 33 +/- 13 bursts/min in control subjects. Total MSNA activity was 1.8 +/- 1.5 AU/min in divers and 1.8 +/- 1.3 AU/min in control subjects. Arterial oxygen saturation did not change during rebreathing, whereas end-tidal CO(2) increased continuously. The slope of the hypercapnic ventilatory and MSNA response was similar in both groups. We conclude that repeated bouts of hypoxemia in elite, healthy breath-holding divers do not lead to sustained sympathetic activation or arterial hypertension. Repeated episodes of hypoxemia may not be sufficient to drive an increase in resting sympathetic activity in the absence of additional comorbidities.

Regression of Asymmetric Upper Extremity Tremor After Liver Transplantation in a Patient With Hepatic Encephalopathy: Case Report.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver failure. Clinically, it can manifests as a wide spectrum of neurological or psychiatric abnormalities. This report presents a case of a 43-year-old male with HE and asymmetric kinetic, postural and resting tremor of upper extremities. Magnetic resonance imaging (MRI) of the brain showed signal abnormalities in numerous areas. The patient underwent liver transplantation and six months after normalization of liver function, tremor as well as brain MRI abnormalities almost completely regressed. This case re-port presents the asymmetric and reversible kinetic, postural and resting tremor of upper extremities as part of the spectrum of neurological abnormalities in HE.

Incidence of Central Nervous System Tumors in Patients Hospitalized at Split University Hospital Centre During a Ten-Year Period (January 1, 2004 - December 31, 2013).

The aim was to evaluate the incidence and characteristics of central nervous system tumors in patients hospitalized at the Department of Neurology, Split University Hospital Centre, during a 10-year period. The study included data on 859 patients with the diagnosis of central nervous system (CNS) tumor. Diagnosis was based on the routine CNS neuroimaging methods (computed tomography/magnetic resonance imaging). Access to patient medical records provided demographic and clinical data, continued by collection of data on potential lethal outcome of patients at the Registrar's Office. The study was conducted at the Department of Neurology, Split University Hospital Centre, from January 1, 2004 to December 31, 2013. There were 448 male and 411 female patients. Median age at the diagnosis was 65 (range, 18-95) years. Primary CNS tumors were diagnosed in 527 patients, including 30 primary recurrent tumors, whereas 328 patients had metastatic tumors; in 4 cases, it was impossible to determine whether the tumor was a primary one or metastasis based on CNS neuroimaging. The primary tumors proved to be more common than the metastatic ones (χ2-test, p<0.05). Multiple tumor transplants were more common than solitary (211 vs. 117; the conclusion was made at a 95% level of confidence; χ2-test, p<0.05). The majority of metastases originated from the lung (bronchus and pleura cancer; 46.41%; χ2-test, p<0.05; 95% CI). The most common localization of CNS tumors was supratentorial. Based on the double-logarithmic model, we proved with statistical significance that there was an increase in the incidence of CNS tumors (p=0.001). The most common tumors studied were supratentorially localized meningiomas.

Correlation analysis of visual analogue scale and measures of walking ability in multiple sclerosis patients.

Walking limitation assessment in multiple sclerosis patients (MSPs) is a demanding task, especially in the clinical setting. The aim of this study is to correlate the visual analogue scale (VAS), a simple method for measuring subjective experience, with measures of walking ability used in clinical research of MS. The study included 82 ambulatory MSPs who have resided in the local community. The applied measures of walking ability were the following: the single-item and patient-rated Walking Ability Visual Analogue Scale (WA-VAS), the Expanded Disability Status Scale (EDSS), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST), the 2 min timed walk (2 min TW), the Multiple Sclerosis Walking Scale-12 (MSWS-12), and step activity monitor accelerometer (SAM) during 7 day period. The SAM analysis included the average daily step count, the average steps/min of the highest 1 min of a day, and the average steps/min of the highest continuous 60 min of a day. The WA-VAS scores significantly and strongly correlated with EDSS (ρ = 0.679, P < 0.001), 25FWT (ρ = 0.606, P < 0.001), SSST (ρ = 0.729, P < 0.001), 2 min TW (ρ = -0.643, P < 0.001), MSWS-12 (ρ = 0.746, P < 0.001), average daily step count (ρ = -0.507, P < 0.001), average steps/min of the highest 1 min of a day (ρ = -0.544, P < 0.001), and average steps/min of the highest continuous 60 min of a day (ρ = -0.473, P < 0.001). Correlations between WA-VAS and measures of walking ability used in clinical research of MS were satisfactory. The results obtained in this research indicate that the WA-VAS could be an instrument for simple measurement of walking limitations in MSPs in the clinical setting.

Sympathetic and cardiovascular responses to glossopharyngeal insufflation in trained apnea divers.

Glossopharyngeal insufflation (lung packing) is a common maneuver among experienced apnea divers by which additional air is pumped into the lungs. It has been shown that packing may compromise cardiovascular homeostasis. We tested the hypothesis that the packing-mediated increase in intrathoracic pressure enhances the baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA) in response to an exaggerated drop in cardiac output (CO). We compared changes in hemodynamics and MSNA (peroneal microneurography) during maximal breath-holds without and with prior moderate packing (0.79 ± 0.40 liters) in 14 trained divers (12 men, 2 women, 26.7 ± 4.5 yr, body mass index 24.8 ± 2.4 kg/m(2)). Packing did not change apnea time (3.8 ± 1.0 vs. 3.8 ± 1.2 min), hemoglobin oxygen desaturation (-17.6 ± 12.3 vs. -18.7 ± 12.8%), or the reduction in CO (1 min: -3.65 ± 1.83 vs. -3.39 ± 1.96 l/min; end of apnea: -2.44 ± 1.33 vs. -2.16 ± 1.44 l/min). On the other hand, packing dampened the early, i.e., 1-min increase in mean arterial pressure (MAP, 1 min: 9.2 ± 8.3 vs. 2.4 ± 11.0 mmHg, P < 0.01) and in total peripheral resistance (relative TPR, 1 min: 2.1 ± 0.5 vs. 1.9 ± 0.5, P < 0.05) but it augmented the concomitant rise in MSNA (1 min: 28.0 ± 11.7 vs. 39.4 ± 12.7 bursts/min, P < 0.001; 32.8 ± 16.4 vs. 43.9 ± 14.8 bursts/100 heart beats, P < 0.01; 3.3 ± 2.1 vs. 4.8 ± 3.2 au/min, P < 0.05). We conclude that the early sympathoactivation 1 min into apnea after moderate packing is due to mechanisms other than excessive reduction in CO. We speculate that lower MAP despite increased MSNA after packing might be explained by vasodilator substances released by the lungs. This idea should be addressed in future studies.

Risk factors and outcome differences between ischemic and hemorrhagic stroke.

The aim of the study was to justify the hypothesis that risk factors do not differ between ischemic and hemorrhagic stroke. This retrospective study included 1066 stroke patients. The prevalence of risk factors and hospital-based survival were compared between patients with ischemic and hemorrhagic stroke. Data were retrieved from patient records. Statistical analysis was done by use of chi2-test and t-test for dependent samples. The group of hemorrhagic stroke consisted of 70 (47.9%) female and 76 (52.1%) male patients. The group of ischemic stroke included 450 (48.9%) female and 470 (51.1%) male patients. Ischemic stroke patients had a higher prevalence of hypertension (79% vs. 72%), atherosclerotic diseases (50% vs. 34%) and atrial fibrillation (15.5% vs. 4.2%), and were statistically significantly older (72.5 +/-10.4 vs. 65.7 +/- 12.8) than those with hemorrhagic stroke, however, fatal outcome was more common in the latter (26% vs. 17%). In conclusion, data analysis pointed to differences between hemorrhagic and ischemic stroke according to both risk factors and stroke outcome.

Cardiovascular regulation during apnea in elite divers.

Involuntary apnea during sleep elicits sustained arterial hypertension through sympathetic activation; however, little is known about voluntary apnea, particularly in elite athletes. Their physiological adjustments are largely unknown. We measured blood pressure, heart rate, hemoglobin oxygen saturation, muscle sympathetic nerve activity, and vascular resistance before and during maximal end-inspiratory breath holds in 20 elite divers and in 15 matched control subjects. At baseline, arterial pressure and heart rate were similar in both groups. Maximal apnea time was longer in divers (1.7+/-0.4 versus 3.9+/-1.1 minutes; P<0.0001), and it was accompanied by marked oxygen desaturation (97.6+/-0.7% versus 77.6+/-13.9%; P<0.0001). At the end of apnea, divers showed a >5-fold greater muscle sympathetic nerve activity increase (P<0.01) with a massively increased pressor response compared with control subjects (9+/-5 versus 32+/-15 mm Hg; P<0.001). Vascular resistance increased in both groups, but more so in divers (79+/-46% versus 140+/-82%; P<0.01). Heart rate did not change in either group. The rise in muscle sympathetic nerve activity correlated with oxygen desaturation (r(2)=0.26; P<0.01) and with the increase in mean arterial pressure (r(2)=0.40; P<0.0001). In elite divers, breath holds for several minutes result in an excessive chemoreflex activation of sympathetic vasoconstrictor activity. Extensive sympathetically mediated peripheral vasoconstriction may help to maintain adequate oxygen supply to vital organs under asphyxic conditions that untrained subjects are not able to tolerate voluntarily. Our results are relevant to conditions featuring periodic apnea.