Renata Pecotic

The evaluation of the Croatian version of the Epworth sleepiness scale and STOP questionnaire as screening tools for obstructive sleep apnea syndrome

PurposeGrowing awareness of obstructive sleep apnea syndrome (OSAS) has increased the need for concise and reliable screening tools. The Epworth sleepiness scale (ESS) has been validated in numerous languages and ethnic groups, since it was originally designed for the English-speaking population. The STOP questionnaire was developed as a novel OSAS screening tool in surgical patients, but has not been validated in the general population. The present study was undertaken to provide reliable and validated ESS in the Croatian language and to evaluate the ESS and STOP as screening instruments for OSAS.MethodsThe Croatian version of ESS and STOP questionnaire was administered to 217 patients referred to the Split Sleep Medicine Center and 208 healthy control subjects. Test–retest reliability was investigated in 20 healthy subjects.ResultsThe ESS score was significantly higher for the patients referred to the Split Sleep Medicine Center compared to the control group (8.2 ± 5.0 vs. 5.9 ± 3.8, p < 0.001). Cronbachs alpha coefficient for the ESS Croatian version was 0.84 indicating an excellent internal consistency. Reproducibility revealed no significant difference in each item or in the total ESS scores. Receiver operating curve of the ESS for identification of cases with AHI >5/h was 0.64, and for the STOP questionnaire, it was 0.84.ConclusionsBoth ESS and STOP questionnaires successfully distinguished healthy subjects from subjects with OSAS. The STOP questionnaire had better probability to correctly predict high-risk patients for OSAS compared to ESS. We propose that the STOP questionnaire could be used as an easy-to-use and accurate screening tool in identification of patients with risk for OSAS in the general population, but it has not been tested in the Croatian population yet.

Propofol abolished the phrenic long-term facilitation in rats

The aim was to investigate the effect of propofol anesthesia on the phrenic long-term facilitation (pLTF) in rats. We hypothesized that pLTF would be abolished during propofol-compared with urethane anesthesia. Fourteen adult, male, anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats (seven per group), were exposed to the acute intermittent hypoxia (AIH) protocol. Peak phrenic nerve activity (PNA), burst frequency (f), and breathing rhythm parameters (Ti, Te, Ttot) were analyzed during the first hypoxia (TH1), as well as at 15 (T15), 30 (T30), and 60min (T60) after the final hypoxic episode, and compared to the baseline values. In propofol-anesthetized rats no significant changes of PNA were recorded after the last hypoxic episode, i.e. no pLTF was induced. There was a significant increase of PNA (59.4+/-6.6%, P<0.001) in urethane-anesthetized group at T60. AIH did not elicit significant changes in f, Ti, Te, Ttot in either group at T15, T30, and T60. The pLTF, elicited by AIH, was induced in the urethane-anesthetized rats. On the contrary, pLTF was abolished in the propofol-anesthetized rats.

The acute hypoxic ventilatory response under halothane, isoflurane, and sevoflurane anaesthesia in rats*

The relative order of potency of anaesthetic agents on the hypoxic ventilatory response has been tested in humans, but animal data are sparse. We examined the effects of 1.4, 1.6, 1.8, and 2.0 MAC halothane, isoflurane, and sevoflurane on phrenic nerve activity in euoxia (baseline) and during acute normocapnic hypoxia (inspired oxygen fraction 0.09) in adult male Sprague‐Dawley rats. With halothane, all animals became apnoeic even in euoxia, and the hypoxic response was completely abolished at all anaesthetic levels. With isoflurane, 5 of 14 animals exhibited phrenic nerve activity in euoxia at 1.4 MAC and demonstrated a hypoxic response (302% of baseline activity), but all became apnoeic and lost the hypoxic response at higher doses. With sevoflurane, phrenic nerve activity and a hypoxic response was preserved in at least some animals at all doses (i.e. even the highest dose of 2.0 MAC). Similar to the rank order of potency previously observed in humans, the relative order of potency of depression of the hypoxic ventilatory response in rats was halothane (most depressive) > isoflurane > sevoflurane (p = 0.01 for differences between agents).

Improvement of Cognitive and Psychomotor Performance in Patients with Mild to Moderate Obstructive Sleep Apnea Treated With Mandibular Advancement Device: A Prospective 1-Year Study.

STUDY OBJECTIVES This study aimed to provide the evidence on effect of mandibular advancement device (MAD) therapy on long-term cognitive and psychomotor performance, excessive daytime sleepiness, and quality of life in patients with mild to moderate obstructive sleep apnea (OSA). METHODS A total of 15 patients with mild to moderate OSA were treated with MAD therapy and they were followed up after 3 mo and 1 y of therapy. The patients were tested on three different tests of cognitive and psychomotor performance using the computer-based system Complex Reactionmeter Drenovac (CRD-series) at baseline and at the time of follow-up, and the 36-Item Short Form Health Survey (SF-36) questionnaire and Epworth Sleepiness Scale were used to assess their quality of life and excessive daytime sleepiness, respectively. RESULTS The mean apnea-hypopnea index (AHI) decreased significantly from 22.9 ± 5.9 events/h at baseline, to 9.7 ± 4.5 events/h after 1 y of MAD therapy (p < 0.001). There was significant improvement on all three CRD-series tests used after 1 y of MAD therapy, considering total test solving time (TTST) and minimal single task solving time (MinT), whereas total number of errors committed during the tests (TE) remained unchanged. Self-reported measures, excessive daytime sleepiness, and three domains of quality of life, social functioning, general health perception, and health change following MAD therapy showed significant improvements after 1 y of MAD therapy. CONCLUSIONS This study demonstrates significant improvements in cognitive and psychomotor performance, particularly in the domain of perceptive abilities, convergent thinking (constructing and solving simple mathematical tasks) and psychomotor reaction times, excessive daytime sleepiness, and quality of life in patients with mild to moderate OSA following MAD therapy.

Role of 5-HT1A receptors in induction and preservation of phrenic long-term facilitation in rats

The aim was to investigate the role of 5-HT₁(A) receptor activation in induction and preservation of phrenic long-term facilitation (pLTF) at two different time points, before exposures to episodic hypoxia and after pLTF was induced. Adult, male, urethane anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypoxia (AIH) protocol. Experimental groups of animals received an intravenous injection of WAY-100635, before the onset of the first hypoxic stimulus (WAY0), and after pLTF was induced (WAY60). Peak phrenic nerve activity (pPNA), burst frequency (f), and respiratory rhythm parameters were analyzed during the five hypoxic exposures (TH1-5), as well as at 15 min (T15), 30 min (T30), and 60 min (T60) after the end of the last hypoxic episode. In the control group, pPNA was elevated from baseline (121.6 ± 7.3%, P < 0.001) at 60 min after episodic hypoxia indicating pLTF. Administration of WAY-100635 prior to hypoxic stimulation prevented the induction of pLTF. Additionally, administration of WAY-100635 after pLTF developed impaired preservation of pLTF. In conclusion, there is an important role for 5-HT₁(A) receptors in induction as well as in preservation of pLTF in urethane anesthetized rats.

Intermittent hypercapnia-induced phrenic long-term depression is revealed after serotonin receptor blockade with methysergide in anaesthetized rats.

What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long‐term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long‐term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long‐term depression was revealed in animals pretreated with the serotonin broad‐spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats.

Acute intermittent hypoxia induces phrenic long‐term facilitation which is modulated by 5‐HT1A receptor in the caudal raphe region of the rat

Obstructive sleep apnoea (OSA) is characterized by periods of upper airway collapse accompanied by repeated episodes of hypoxia. In experimental animals repeated bouts of hypoxia may evoke sustained augmentation of phrenic nerve activity, known as phrenic long‐term facilitation (pLTF). This form of physiological compensation might contribute to stable breathing, minimizing the occurrence of apnoeas and/or hypopnoeas during sleep in patients with OSA. Serotonin (5‐HT) has been shown to modulate respiratory neuronal activity, possibly via projections originating in the raphe nuclei. Our model focuses on the effects of 5‐HT1A receptors blockade by selective antagonist WAY‐100635 into the caudal raphe region on phrenic long‐term facilitation after exposure to acute intermittent hypoxia (AIH) episodes. Adult, male, urethane‐anaesthetized, vagotomized, paralyzed and mechanically ventilated Sprague–Dawley rats were exposed to AIH protocol. Experimental group received microinjection of WAY‐100635 into the caudal raphe nucleus, whereas the control group received saline into the same site. Peak phrenic nerve activity and respiratory rhythm parameters were analysed during five hypoxic episodes, as well as at 15, 30 and 60 min after the end of hypoxias. In the control group, 1 h post‐hypoxia pLTF was developed. Microinjections of selective 5‐HT1A receptor antagonist WAY‐100635 into the raphe nuclei prior to the AIH protocol prevented induction of pLTF. These results suggest that 5‐HT1A receptor activation at supraspinal level is important for induction of pLTF, which is suggested to be an important respiratory neuroplasticity model in animal studies that possibly correlates with OSA in humans.

The relationship between sleep habits and academic performance in dental students in Croatia

INTRODUCTION It is well accepted that sleep and lifestyle habits affect academic success in students. However, sleep patterns and sleep problems amongst dental students have been insufficiently addressed in the literature. The purpose of this study was to evaluate sleep habits of dental students and the relationship between sleep habits and academic performance. MATERIALS AND METHODS A self-administered questionnaire on sleep habits, academic performance and lifestyle was administered. The participants were 447 dental students from Split University Dental Medicine School and Zagreb University Dental Medicine School from the six academic years. The subjects were classified into two groups based on academic success (high-performing vs. low-performing students) for comparison of sleep and lifestyle habits. RESULTS Amongst the whole group of students, average bedtime and wake time during weekday was significantly earlier compared with weekend. Main findings indicate that students with high academic performance had earlier bedtimes during weekdays and weekends, earlier wake times during weekends and shorter sleep latency compared with low academic performing students. CONCLUSION Self-reported academic performance of dental students in Croatia is associated with timing of sleep and wakefulness, rather than with total sleep time duration.

Influence of the wars in Croatia and Bosnia and Herzegovina on the incidence and outcome of singleton premature births in the Split University Hospital

To investigate the influence of the wars in Croatia and Bosnia and Herzegovina on incidence and perinatal outcome of singleton preterm births at the Department of Gynecology and Obstetrics in the Split University Hospital. Data were collected by reviewing patients’ files at the Department of Gynecology and Obstetrics from three periods: the three years before the war (1988–1990), during the war (1992–1994), and after the war (1996–1998). A total of 2,358 patients’ files of singleton preterm delivery were analyzed. Singleton preterm delivery rate decreased during the war (5.02%) and post-war period (4.74%) compared to the pre-war period (6.19%). Stillbirth and early neonatal mortality rates of singleton premature babies significantly increased during the war to 226%, compared to 193% before the war and 134% after the war. Early neonatal mortality rate was 215% during the war, 209% in the pre-war period, and 156% after the war. Despite the continuous decrease in singleton preterm birth rate throughout the observed periods, the increase in stillbirth rate and early neonatal mortality rate during the war might have been caused by the war. This may be due to primary gynecological care being inadequate for many pregnant women.

Phrenic long-term depression evoked by intermittent hypercapnia is modulated by serotonergic and adrenergic receptors in raphe nuclei

Intermittent hypercapnia evokes prolonged depression of phrenic nerve activity (phrenic long-term depression, pLTD). This study was undertaken to investigate the role of 5-HT and α2-adrenergic receptors in the initiation of pLTD. Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to a protocol of acute intermittent hypercapnia (AIHc; 5 episodes of 15% CO2 in air, each episode lasting 3 min). The experimental group received microinjection of the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), the broad-spectrum 5-HT antagonist methysergide, or the α2-adrenergic antagonist yohimbine, whereas the control group received microinjection of 0.9% saline into the caudal raphe region. Peak phrenic nerve activity (pPNA) and burst frequency ( f) were analyzed during baseline (T0), during 5 hypercapnic episodes (THc1-THc5), and at 15, 30, and 60 min after the end of the last hypercapnic episode. In the control group, pPNA decreased 60 min after the end of the last hypercapnic episode compared with baseline values, i.e., pLTD developed ( P = 0.023). In the 8-OH-DPAT group, pPNA significantly decreased at T15, T30, and T60 compared with baseline values, i.e., pLTD developed ( P = 0.01). In the methysergide and yohimbine groups, AIHc did not evoke significant changes of the pPNA at T15, T30, and T60 compared with baseline values. In conclusion, activation of 5-HT1A receptors accentuated induction of pLTD, whereas blockade of α2-adrenergic receptors prevented development of pLTD following AIHc in anesthetized rats. These results suggest that chemical modulation of 5-HT and α2-adrenergic receptors in raphe nuclei affects hypercapnia-induced pLTD, offering important insights in understanding the mechanisms involved in development of respiratory plasticity. NEW & NOTEWORTHY Hypercapnia is a concomitant feature of many breathing disorders, including obstructive sleep apnea. In this study, acute intermittent hypercapnia evoked development of phrenic long-term depression (pLTD) 60 min after the last hypercapnic episode that was preserved if the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide was microinjected in the caudal raphe region before the hypercapnic stimulus. This study highlights that both 5-HT and adrenergic receptor activation is needed for induction of pLTD in urethane-anesthetized rats following intermittent hypercapnia exposure.